Trial Outcomes & Findings for mTBI Mechanisms of Action of HBO2 for Persistent Post-Concussive Symptoms (NCT NCT01611194)

NCT ID: NCT01611194

Last Updated: 2018-11-21

Results Overview

Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 71 participants
• Primary outcome timeframe: months 3, 6, 4, 5 and 7-12. Extended f/u up to 36 months
• Results posted on: 2018-11-21

Participant Flow

Participants were recruited from military sites from Sept 2012 to May 2014.

Participant milestones

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Overall Study STARTED	36	35
Overall Study COMPLETED	36	32
Overall Study NOT COMPLETED	0	3

Reasons for withdrawal

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	0	1
Overall Study drug use	0	1

Baseline Characteristics

mTBI Mechanisms of Action of HBO2 for Persistent Post-Concussive Symptoms

Baseline characteristics by cohort

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=36 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=35 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).	Total n=71 Participants Total of all reporting groups
Age, Continuous	34.8 years STANDARD_DEVIATION 8.3 • n=5 Participants	30.8 years STANDARD_DEVIATION 5.5 • n=7 Participants	32.8 years STANDARD_DEVIATION 7.3 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	34 Participants n=7 Participants	70 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants	29 Participants n=7 Participants	58 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants	28 Participants n=7 Participants	58 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	36 Participants n=5 Participants	35 Participants n=7 Participants	71 Participants n=5 Participants
Education Less than high school diploma	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Education High school diploma	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Education Some college	13 Participants n=5 Participants	23 Participants n=7 Participants	36 Participants n=5 Participants
Education College degree	11 Participants n=5 Participants	5 Participants n=7 Participants	16 Participants n=5 Participants
Education Graduare degree	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Military Status Active duty	35 Participants n=5 Participants	33 Participants n=7 Participants	68 Participants n=5 Participants
Military Status Veteran	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Time From Most Recent Qualifying Mild Traumatic Brain Injury (mTBI)	25.6 months STANDARD_DEVIATION 17.1 • n=5 Participants	25.5 months STANDARD_DEVIATION 15.4 • n=7 Participants	25.6 months STANDARD_DEVIATION 16.2 • n=5 Participants
Most Recent Qualifying mTBI 3 Months to 1 Year 3 months to 1 year	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Most Recent Qualifying mTBI 3 Months to 1 Year >1year to 5 years	24 Participants n=5 Participants	27 Participants n=7 Participants	51 Participants n=5 Participants
Number of Lifetime mTBIs	3.6 mTBIs STANDARD_DEVIATION 3.2 • n=5 Participants	3.7 mTBIs STANDARD_DEVIATION 2.3 • n=7 Participants	3.6 mTBIs STANDARD_DEVIATION 2.8 • n=5 Participants
Lifetime mTBI History Blast injuries	15 Participants n=5 Participants	8 Participants n=7 Participants	23 Participants n=5 Participants
Lifetime mTBI History Blunt force head injuries only	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Lifetime mTBI History Combination of blast and blunt force injuries	14 Participants n=5 Participants	20 Participants n=7 Participants	34 Participants n=5 Participants
Most Recent Qualifying Injury Blast injury	23 Participants n=5 Participants	23 Participants n=7 Participants	46 Participants n=5 Participants
Most Recent Qualifying Injury Blunt force head injury	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Military Rank E1-E10	31 Participants n=5 Participants	35 Participants n=7 Participants	66 Participants n=5 Participants
Military Rank O-1 to O-10/W-1 to W-5	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Military Branch Army	27 Participants n=5 Participants	28 Participants n=7 Participants	55 Participants n=5 Participants
Military Branch Marines	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Military Branch Navy, Air Force, and Coast Guard	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Number of Combat Deployments	3.4 deployments STANDARD_DEVIATION 2.8 • n=5 Participants	2.2 deployments STANDARD_DEVIATION 1.7 • n=7 Participants	2.8 deployments STANDARD_DEVIATION 2.4 • n=5 Participants
Common Medication Usage SSRI/SNRIs	12 participants n=5 Participants	10 participants n=7 Participants	22 participants n=5 Participants
Common Medication Usage Hypnotic or sleep aid	16 participants n=5 Participants	15 participants n=7 Participants	31 participants n=5 Participants
Common Medication Usage Daily pain medication	22 participants n=5 Participants	21 participants n=7 Participants	43 participants n=5 Participants
Common Medication Usage Episodic migraine medication	16 participants n=5 Participants	14 participants n=7 Participants	30 participants n=5 Participants
Common Medication Usage Fish oil or omega-3 fatty acid	9 participants n=5 Participants	8 participants n=7 Participants	17 participants n=5 Participants
Common Alternative Therapy Usage Psychotherapy	12 participants n=5 Participants	7 participants n=7 Participants	19 participants n=5 Participants
Common Alternative Therapy Usage Counseling	16 participants n=5 Participants	12 participants n=7 Participants	28 participants n=5 Participants
Common Alternative Therapy Usage Physical therapy	14 participants n=5 Participants	20 participants n=7 Participants	34 participants n=5 Participants

PRIMARY outcome

Timeframe: months 3, 6, 4, 5 and 7-12. Extended f/u up to 36 months

Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=36 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=35 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Summary of Treatment-Emergent Adverse Events Barotitis media	13 Participants	5 Participants
Summary of Treatment-Emergent Adverse Events Sinus barotrauma	5 Participants	3 Participants
Summary of Treatment-Emergent Adverse Events Contusion	3 Participants	3 Participants
Summary of Treatment-Emergent Adverse Events Ligament sprain	0 Participants	5 Participants
Summary of Treatment-Emergent Adverse Events Back pain	3 Participants	2 Participants
Summary of Treatment-Emergent Adverse Events Neck pain	0 Participants	4 Participants
Summary of Treatment-Emergent Adverse Events Dizziness	5 Participants	1 Participants
Summary of Treatment-Emergent Adverse Events Headache	4 Participants	2 Participants
Summary of Treatment-Emergent Adverse Events Nasal congestion	5 Participants	3 Participants
Summary of Treatment-Emergent Adverse Events Dyspnea	4 Participants	1 Participants
Summary of Treatment-Emergent Adverse Events Epistaxis	2 Participants	2 Participants
Summary of Treatment-Emergent Adverse Events Sinus congestion	2 Participants	2 Participants
Summary of Treatment-Emergent Adverse Events Eye disorders	10 Participants	7 Participants
Summary of Treatment-Emergent Adverse Events Nausea	4 Participants	1 Participants
Summary of Treatment-Emergent Adverse Events Rash	0 Participants	3 Participants
Summary of Treatment-Emergent Adverse Events Vascular disorders	3 Participants	0 Participants
Summary of Treatment-Emergent Adverse Events Congenital, familial and genetic disorders	1 Participants	0 Participants
Summary of Treatment-Emergent Adverse Events Endocrine disorders	1 Participants	0 Participants
Summary of Treatment-Emergent Adverse Events Hepatobiliary disorders	1 Participants	0 Participants
Summary of Treatment-Emergent Adverse Events Immune system disorders	0 Participants	1 Participants
Summary of Treatment-Emergent Adverse Events Neoplasms benign, malignant and unspecified	0 Participants	1 Participants
Summary of Treatment-Emergent Adverse Events Muscle strain	1 Participants	3 Participants
Summary of Treatment-Emergent Adverse Events Upper respiratory tract infection	13 Participants	9 Participants
Summary of Treatment-Emergent Adverse Events Gastroenteritis	1 Participants	5 Participants
Summary of Treatment-Emergent Adverse Events Sinusitis	3 Participants	4 Participants
Summary of Treatment-Emergent Adverse Events Nasopharyngitis	3 Participants	2 Participants
Summary of Treatment-Emergent Adverse Events Arthralgia	4 Participants	2 Participants
Summary of Treatment-Emergent Adverse Events Suicidal ideation	2 Participants	2 Participants
Summary of Treatment-Emergent Adverse Events Investigations	4 Participants	3 Participants
Summary of Treatment-Emergent Adverse Events Vertigo	3 Participants	3 Participants
Summary of Treatment-Emergent Adverse Events General and administration site conditions	3 Participants	1 Participants
Summary of Treatment-Emergent Adverse Events Metabolism and nutrition disorders	3 Participants	2 Participants
Summary of Treatment-Emergent Adverse Events Renal and urinary disorders	3 Participants	0 Participants

PRIMARY outcome

Timeframe: months 3, 6, 4, 5 and 7-12. Extended f/u up to 36 months

Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=36 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=35 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Summary of Study Intervention-Related Adverse Events Barotitis media	11 Participants	5 Participants
Summary of Study Intervention-Related Adverse Events Sinus barotrauma	5 Participants	4 Participants
Summary of Study Intervention-Related Adverse Events Dizziness	1 Participants	1 Participants
Summary of Study Intervention-Related Adverse Events Headache	1 Participants	2 Participants
Summary of Study Intervention-Related Adverse Events Somnolence	1 Participants	1 Participants
Summary of Study Intervention-Related Adverse Events Dyspnea	2 Participants	0 Participants
Summary of Study Intervention-Related Adverse Events Hyperventilation	1 Participants	0 Participants
Summary of Study Intervention-Related Adverse Events Anxiety	1 Participants	0 Participants
Summary of Study Intervention-Related Adverse Events Myopia	1 Participants	1 Participants
Summary of Study Intervention-Related Adverse Events Eye pruritus	0 Participants	1 Participants
Summary of Study Intervention-Related Adverse Events Vertigo	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline

RPQ/RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. Scale compares any current symptoms to pre-injury levels to account for potential symptom exacerbation due to the TBI. The RPQ is the most commonly used clinical measure for mild TBI research because it is simple and reflects psychosocial function. The RPQ is intended to measure the presence and severity of 16 of the most commonly reported post-concussion symptoms found in the literature. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-3 and RPQ-13 domain scores are presented separately. For each of the RPQ-3, RPQ-13, and RPQ total scales, the scores were derived by totaling the corresponding question scores for each domain.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=36 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=35 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ, RPQ3 and RPQ13) - Baseline (ITT Population) RPQ Total Score	34.8 RPQ scores Standard Deviation 13.1	28.2 RPQ scores Standard Deviation 13.5
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ, RPQ3 and RPQ13) - Baseline (ITT Population) RPQ-13 Score	29.0 RPQ scores Standard Deviation 11.0	23.7 RPQ scores Standard Deviation 11.4
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ, RPQ3 and RPQ13) - Baseline (ITT Population) RPQ-3 Score	5.8 RPQ scores Standard Deviation 2.9	4.5 RPQ scores Standard Deviation 2.6

SECONDARY outcome

Timeframe: Baseline

Population: PP was defined as subs who completed 20 chamber sessions and week13 f/u. PP was also restricted to subs who didn't report illicit drug use following randomization. 67 subs satisfied the PP, 35/36 HBO2 and 32/35 sham. 4 were excluded from the PP population, 3 excluded because they completed \<20 sessions,1 because of illicit drug use during study.

RPQ/RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. Scale compares any current symptoms to pre-injury levels to account for potential symptom exacerbation due to the TBI. The RPQ is the most commonly used clinical measure for mild TBI research because it is simple and reflects psychosocial function. The RPQ is intended to measure the presence and severity of 16 of the most commonly reported post-concussion symptoms found in the literature. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-3 and RPQ-13 domain scores are presented separately. For each of the RPQ-3, RPQ-13, and RPQ total scales, the scores were derived by totaling the corresponding question scores for each domain.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=35 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=32 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ, RPQ3 and RPQ13) - Baseline (Per Protocol (PP) Population) RPQ Total Score	34.7 RPQ scores Standard Deviation 13.3	27.3 RPQ scores Standard Deviation 12.9
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ, RPQ3 and RPQ13) - Baseline (Per Protocol (PP) Population) RPQ-3 Score	5.8 RPQ scores Standard Deviation 2.9	4.5 RPQ scores Standard Deviation 2.5
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ, RPQ3 and RPQ13) - Baseline (Per Protocol (PP) Population) RPQ-13 Score	28.9 RPQ scores Standard Deviation 11.1	22.8 RPQ scores Standard Deviation 11.0

SECONDARY outcome

Timeframe: Baseline to week 13, Months 6 and 12

Population: 1 subject in HBO2 missed the 6 month visit and 2 subjects missed the 12 month visit. 1 subject in the sham missed the week 13 visit and, 1 subject missed the month 6 visit and 3 subjects withdrew by month 12

RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. Scale compares any current symptoms to pre-injury levels to account for potential symptom exacerbation due to the TBI. The RPQ is the most commonly used clinical measure for mild TBI research because it is simple and reflects psychosocial function. The RPQ is intended to measure the presence and severity of 16 of the most commonly reported post-concussion symptoms found in the literature. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. The scores were derived by totaling the corresponding question scores for each domain and it's change from baseline.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=36 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=35 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (ITT Population) Week 13 change score	-0.7 RPQ scores Standard Deviation 14.6	5.8 RPQ scores Standard Deviation 12.4
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (ITT Population) Month 6 change score	-4.3 RPQ scores Standard Deviation 14.0	2.6 RPQ scores Standard Deviation 11.6
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (ITT Population) Month 12 change score	5.7 RPQ scores Standard Deviation 14.7	5.5 RPQ scores Standard Deviation 12.4

SECONDARY outcome

Timeframe: Baseline to week 13, Months 6 and 12

Population: 1 subject in HBO2 missed the 6 month visit and 2 subjects missed the 12 month visit. 1 subject in the sham missed the week 13 visit and, 1 subject missed the month 6 visit and 3 subjects withdrew by month 12

RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. Scale compares any current symptoms to pre-injury levels to account for potential symptom exacerbation due to the TBI. The RPQ is the most commonly used clinical measure for mild TBI research because it is simple and reflects psychosocial function. The RPQ is intended to measure the presence and severity of 16 of the most commonly reported post-concussion symptoms found in the literature. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. Analyses of the RPQ-3 domain scores are presented separately. For the RPQ-3 total scales, the scores were derived by totaling the corresponding question scores for each domain and it's change from baseline.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=36 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=35 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (ITT Population) Week 13 change score	-0.3 RPQ scores Standard Deviation 2.7	1.2 RPQ scores Standard Deviation 2.2
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (ITT Population) Month 6 change score	-1.4 RPQ scores Standard Deviation 2.7	0.3 RPQ scores Standard Deviation 2.2
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (ITT Population) Month 12 change score	0.5 RPQ scores Standard Deviation 2.9	0.5 RPQ scores Standard Deviation 2.6

SECONDARY outcome

Timeframe: Baseline to week 13, Months 6 and 12

Population: 1 subject in HBO2 missed the 6 month visit and 2 subjects missed the 12 month visit. 1 subject in the sham missed the week 13 visit and, 1 subject missed the month 6 visit and 3 subjects withdrew by month 12

RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. Scale compares any current symptoms to pre-injury levels to account for potential symptom exacerbation due to the TBI. The RPQ is the most commonly used clinical measure for mild TBI research because it is simple and reflects psychosocial function. The RPQ is intended to measure the presence and severity of 16 of the most commonly reported post-concussion symptoms found in the literature. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-13 domain scores are presented separately. For RPQ-13 total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=36 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=35 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (ITT Population) Month 6 change score	-3.0 RPQ scores Standard Deviation 11.9	2.3 RPQ scores Standard Deviation 9.9
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (ITT Population) Month 12 change score	5.2 RPQ scores Standard Deviation 12.7	5.0 RPQ scores Standard Deviation 10.4
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (ITT Population) Week 13 change score	-0.4 RPQ scores Standard Deviation 12.3	4.7 RPQ scores Standard Deviation 11.1

SECONDARY outcome

Timeframe: Baseline to week 13, Months 6 and 12

Population: PP was defined as subs who completed 20 chamber sessions and week13 f/u. PP was also restricted to subs who didn't report illicit drug use following randomization. 67 subs satisfied the PP, 35/36 HBO2 and 32/35 sham. 4 were excluded from the PP population, 3 excluded because they completed \<20 sessions,1 because of illicit drug use during study.

RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. Scale compares any current symptoms to pre-injury levels to account for potential symptom exacerbation due to the TBI. The RPQ is the most commonly used clinical measure for mild TBI research because it is simple and reflects psychosocial function. The RPQ is intended to measure the presence and severity of 16 of the most commonly reported post-concussion symptoms found in the literature. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. For the RPQ total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=35 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=32 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (Per Protocol (PP) Population) Week 13 change score	-1.0 RPQ scores Standard Deviation 14.7	6.1 RPQ scores Standard Deviation 12.6
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (Per Protocol (PP) Population) Month 6 change score	-4.3 RPQ scores Standard Deviation 14.0	3.2 RPQ scores Standard Deviation 11.3
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (Per Protocol (PP) Population) Month 12 change score	5.8 RPQ scores Standard Deviation 14.9	5.5 RPQ scores Standard Deviation 12.6

SECONDARY outcome

Timeframe: Baseline to week 13, Months 6 and 12

Population: PP was defined as subs who completed 20 chamber sessions and week13 f/u. PP was also restricted to subs who didn't report illicit drug use following randomization. 67 subs satisfied the PP, 35/36 HBO2 and 32/35 sham. 4 were excluded from the PP population, 3 excluded because they completed \<20 sessions,1 because of illicit drug use during study.

RPQ/RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. Scale compares any current symptoms to pre-injury levels to account for potential symptom exacerbation due to the TBI. The RPQ is the most commonly used clinical measure for mild TBI research because it is simple and reflects psychosocial function. The RPQ is intended to measure the presence and severity of 16 of the most commonly reported post-concussion symptoms found in the literature. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. For the RPQ-3total scale, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=35 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=32 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (Per Protocol (PP) Population) Week 13 change score	-0.4 RPQ scores Standard Deviation 2.8	1.2 RPQ scores Standard Deviation 2.3
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (Per Protocol (PP) Population) Month 6 change score	-1.4 RPQ scores Standard Deviation 2.7	0.3 RPQ scores Standard Deviation 2.2
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (Per Protocol (PP) Population) Month 12 change score	0.4 RPQ scores Standard Deviation 2.9	0.5 RPQ scores Standard Deviation 2.7

SECONDARY outcome

Timeframe: Baseline to week 13, Months 6 and 12

Population: PP was defined as subs who completed 20 chamber sessions and week13 f/u. PP was also restricted to subs who didn't report illicit drug use following randomization. 67 subs satisfied the PP, 35/36 HBO2 and 32/35 sham. 4 were excluded from the PP population, 3 excluded because they completed \<20 sessions,1 because of illicit drug use during study.

RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. Scale compares any current symptoms to pre-injury levels to account for potential symptom exacerbation due to the TBI. The RPQ is the most commonly used clinical measure for mild TBI research because it is simple and reflects psychosocial function. The RPQ is intended to measure the presence and severity of 16 of the most commonly reported post-concussion symptoms found in the literature. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-13 domain scores are presented separately. The scores were derived by totaling the corresponding question scores for each domain and change from baseline.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=35 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=32 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (Per Protocol (PP) Population) Week 13 change score	-0.7 RPQ scores Standard Deviation 12.4	4.9 RPQ scores Standard Deviation 11.2
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (Per Protocol (PP) Population) Month 6 change score	-3.0 RPQ scores Standard Deviation 11.9	2.9 RPQ scores Standard Deviation 9.5
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (Per Protocol (PP) Population) Month 12 change score	5.4 RPQ scores Standard Deviation 12.8	5.1 RPQ scores Standard Deviation 10.6

SECONDARY outcome

Timeframe: Baseline to 24 months and 36 months

Population: HBO2: 25 subs consented to 24 and 36 month f/u; 23 subs completed month 24 and 9 completed month 36; 2 subs missed 24 month visit. Sham: 17 subs consented to 24 and 36 month f/u. 17 completed month 24 and 5 completed month 36

RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. Scale compares any current symptoms to pre-injury levels to account for potential symptom exacerbation due to the TBI. The RPQ is the most commonly used clinical measure for mild TBI research because it is simple and reflects psychosocial function. The RPQ is intended to measure the presence and severity of 16 of the most commonly reported post-concussion symptoms found in the literature. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. For the RPQ total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=36 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=35 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline: 24 and 36 Months (ITT Population) Baseline to 24 months	1.2 RPQ scores Standard Deviation 18.5	2.9 RPQ scores Standard Deviation 11.9
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline: 24 and 36 Months (ITT Population) Baseline to 36 months	1.4 RPQ scores Standard Deviation 9.0	4.6 RPQ scores Standard Deviation 19.6

SECONDARY outcome

Timeframe: Baseline to 24 months and 36 months

Population: HBO2: 25 subs consented to 24 and 36 month f/u; 23 subs completed month 24 and 9 completed month 36; 2 subs missed 24 month visit. Sham: 17 subs consented to 24 and 36 month f/u. 17 completed month 24 and 5 completed month 36

RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. Scale compares any current symptoms to pre-injury levels to account for potential symptom exacerbation due to the TBI. The RPQ is the most commonly used clinical measure for mild TBI research because it is simple and reflects psychosocial function. The RPQ is intended to measure the presence and severity of 16 of the most commonly reported post-concussion symptoms found in the literature. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. Analyses of the RPQ-3 domain scores are presented separately. For the RPQ-3 total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=36 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=35 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline: 24 and 36 Months (ITT Population) Baseline to 24 months	-0.2 RPQ scores Standard Deviation 3.2	-0.1 RPQ scores Standard Deviation 2.7
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline: 24 and 36 Months (ITT Population) Baseline to 36 months	-0.9 RPQ scores Standard Deviation 2.9	0.8 RPQ scores Standard Deviation 3.0

SECONDARY outcome

Timeframe: Baseline to 24 months and 36 months

Population: HBO2: 25 subs consented to 24 and 36 month f/u; 23 subs completed month 24 and 9 completed month 36; 2 subs missed 24 month visit. Sham: 17 subs consented to 24 and 36 month f/u. 17 completed month 24 and 5 completed month 36

RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. Scale compares any current symptoms to pre-injury levels to account for potential symptom exacerbation due to the TBI. The RPQ is the most commonly used clinical measure for mild TBI research because it is simple and reflects psychosocial function. The RPQ is intended to measure the presence and severity of 16 of the most commonly reported post-concussion symptoms found in the literature. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-13 domain scores are presented separately. For RPQ-13 total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=36 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=35 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline: 24 and 36 Months (ITT Population) Baseline to 36 months	2.0 RPQ scores Standard Deviation 7.5	3.8 RPQ scores Standard Deviation 16.8
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline: 24 and 36 Months (ITT Population) Baseline to 24 months	1.4 RPQ scores Standard Deviation 16.1	3.0 RPQ scores Standard Deviation 9.5

SECONDARY outcome

Timeframe: Baseline to month 24 and month 36

Population: PP was defined as subs who completed 20 chamber sessions and week13 f/u. PP was also restricted to subs who didn't report illicit drug use following randomization. 67 subs satisfied the PP, 35/36 HBO2 and 32/35 sham. 4 were excluded from the PP population, 3 excluded because they completed \<20 sessions,1 because of illicit drug use during study.

RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. Scale compares any current symptoms to pre-injury levels to account for potential symptom exacerbation due to the TBI. The RPQ is the most commonly used clinical measure for mild TBI research because it is simple and reflects psychosocial function. The RPQ is intended to measure the presence and severity of 16 of the most commonly reported post-concussion symptoms found in the literature. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. For the RPQ total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=35 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=32 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (Per Protocol (PP) Population) Baseline to month 24	1.2 RPQ scores Standard Deviation 18.5	2.9 RPQ scores Standard Deviation 11.9
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (Per Protocol (PP) Population) Baseline to month 36	1.4 RPQ scores Standard Deviation 9.0	4.6 RPQ scores Standard Deviation 19.6

SECONDARY outcome

Timeframe: Baseline to month 24 and month 36

Population: PP was defined as subs who completed 20 chamber sessions and week13 f/u. PP was also restricted to subs who didn't report illicit drug use following randomization. 67 subs satisfied the PP, 35/36 HBO2 and 32/35 sham. 4 were excluded from the PP population, 3 excluded because they completed \<20 sessions,1 because of illicit drug use during study.

RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. Scale compares any current symptoms to pre-injury levels to account for potential symptom exacerbation due to the TBI. The RPQ is the most commonly used clinical measure for mild TBI research because it is simple and reflects psychosocial function. The RPQ is intended to measure the presence and severity of 16 of the most commonly reported post-concussion symptoms found in the literature. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. Analyses of the RPQ-3 domain scores are presented separately. For the RPQ-3 total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=35 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=32 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (Per Protocol (PP) Population) Baseline to month 24	-0.2 RPQ scores Standard Deviation 3.2	-0.1 RPQ scores Standard Deviation 2.7
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (Per Protocol (PP) Population) Baseline to month 36	-0.9 RPQ scores Standard Deviation 2.9	0.8 RPQ scores Standard Deviation 3.0

SECONDARY outcome

Timeframe: Baseline to month 24 and month 36

Population: PP was defined as subs who completed 20 chamber sessions and week13 f/u. PP was also restricted to subs who didn't report illicit drug use following randomization. 67 subs satisfied the PP, 35/36 HBO2 and 32/35 sham. 4 were excluded from the PP population, 3 excluded because they completed \<20 sessions,1 because of illicit drug use during study.

RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. Scale compares any current symptoms to pre-injury levels to account for potential symptom exacerbation due to the TBI. The RPQ is the most commonly used clinical measure for mild TBI research because it is simple and reflects psychosocial function. The RPQ is intended to measure the presence and severity of 16 of the most commonly reported post-concussion symptoms found in the literature. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-13 domain scores are presented separately. For RPQ-13 total scales, the scores were derived by totaling the corresponding question scores for each domain change from baseline.

Outcome measures

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=35 Participants Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=32 Participants Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (Per Protocol (PP) Population) Baseline to month 24	1.4 RPQ scores Standard Deviation 16.1	3.0 RPQ scores Standard Deviation 9.5
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (Per Protocol (PP) Population) Baseline to month 36	2.0 RPQ scores Standard Deviation 7.5	3.8 RPQ scores Standard Deviation 16.8

Adverse Events

HBO2 at 1.5 Atomspheres Absolute (ATA)

Serious events: 5 serious events

Other events: 35 other events

Deaths: 0 deaths

Sham Control (1.2 Atomspheres)

Serious events: 3 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=36 participants at risk Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=35 participants at risk Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Psychiatric disorders Post-traumatic stress disorder	5.6% 2/36 • Number of events 2 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	0.00% 0/35 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Psychiatric disorders Psychotic disorder	0.00% 0/36 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	2.9% 1/35 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Psychiatric disorders Suicide attempt	0.00% 0/36 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	2.9% 1/35 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
General disorders Pain	2.8% 1/36 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	0.00% 0/35 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Infections and infestations Cellulitis	0.00% 0/36 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	2.9% 1/35 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Injury, poisoning and procedural complications Fall	2.8% 1/36 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	0.00% 0/35 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Musculoskeletal and connective tissue disorders Osteoarthritis	2.8% 1/36 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	0.00% 0/35 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.

Other adverse events

Measure	HBO2 at 1.5 Atomspheres Absolute (ATA) n=36 participants at risk Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.	Sham Control (1.2 Atomspheres) n=35 participants at risk Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
Metabolism and nutrition disorders Vitamin D deficiency	8.3% 3/36 • Number of events 3 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	2.9% 1/35 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Injury, poisoning and procedural complications Barotitis media	36.1% 13/36 • Number of events 20 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	17.1% 6/35 • Number of events 8 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Injury, poisoning and procedural complications Sinus barotrauma	13.9% 5/36 • Number of events 10 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	11.4% 4/35 • Number of events 9 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Injury, poisoning and procedural complications Contusion	16.7% 6/36 • Number of events 8 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	8.6% 3/35 • Number of events 3 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/36 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	14.3% 5/35 • Number of events 5 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Injury, poisoning and procedural complications Mucsle strain	2.8% 1/36 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	8.6% 3/35 • Number of events 3 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Infections and infestations Upper respiratory tract infection	44.4% 16/36 • Number of events 18 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	28.6% 10/35 • Number of events 13 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Infections and infestations Gastroenteritis	2.8% 1/36 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	17.1% 6/35 • Number of events 7 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Infections and infestations Sinusitis	11.1% 4/36 • Number of events 4 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	11.4% 4/35 • Number of events 4 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Infections and infestations Nasopharyngitis	11.1% 4/36 • Number of events 4 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	8.6% 3/35 • Number of events 3 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Musculoskeletal and connective tissue disorders Back pain	8.3% 3/36 • Number of events 5 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	8.6% 3/35 • Number of events 6 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Musculoskeletal and connective tissue disorders Arthralgia	11.1% 4/36 • Number of events 5 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	5.7% 2/35 • Number of events 3 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/36 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	11.4% 4/35 • Number of events 4 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Musculoskeletal and connective tissue disorders Tendonitis	2.8% 1/36 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	8.6% 3/35 • Number of events 3 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Nervous system disorders Dizziness	16.7% 6/36 • Number of events 7 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	2.9% 1/35 • Number of events 2 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Nervous system disorders Headache	11.1% 4/36 • Number of events 4 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	5.7% 2/35 • Number of events 3 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Respiratory, thoracic and mediastinal disorders Nasal congestion	13.9% 5/36 • Number of events 5 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	11.4% 4/35 • Number of events 5 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Respiratory, thoracic and mediastinal disorders Dyspnea	11.1% 4/36 • Number of events 4 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	2.9% 1/35 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.6% 2/36 • Number of events 2 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	5.7% 2/35 • Number of events 2 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Respiratory, thoracic and mediastinal disorders Sinus congestion	5.6% 2/36 • Number of events 2 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	5.7% 2/35 • Number of events 2 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Gastrointestinal disorders Nausea	11.1% 4/36 • Number of events 5 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	2.9% 1/35 • Number of events 2 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Psychiatric disorders Suicidal ideation	5.6% 2/36 • Number of events 2 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	5.7% 2/35 • Number of events 2 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Eye disorders Eye disorders	30.6% 11/36 • Number of events 14 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	20.0% 7/35 • Number of events 10 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Ear and labyrinth disorders Vertigo	8.3% 3/36 • Number of events 5 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	8.6% 3/35 • Number of events 3 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Skin and subcutaneous tissue disorders Rash	2.8% 1/36 • Number of events 2 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	8.6% 3/35 • Number of events 3 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Investigations Investigations	13.9% 5/36 • Number of events 7 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	8.6% 3/35 • Number of events 4 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Skin and subcutaneous tissue disorders General disorders and administration site conditions	16.7% 6/36 • Number of events 6 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	2.9% 1/35 • Number of events 2 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Vascular disorders Vascular disorders	13.9% 5/36 • Number of events 6 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	0.00% 0/35 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Renal and urinary disorders Renal and urinary disorders	8.3% 3/36 • Number of events 4 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	0.00% 0/35 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Immune system disorders Immune system disorders	2.8% 1/36 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	2.9% 1/35 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Blood and lymphatic system disorders Blood and lymphatic system disorders	2.8% 1/36 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	0.00% 0/35 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Congenital, familial and genetic disorders Congenital, familial and genetic disorders	2.8% 1/36 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	0.00% 0/35 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Endocrine disorders Endocrine disorders	2.8% 1/36 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	0.00% 0/35 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Hepatobiliary disorders Hepatobiliary disorders	2.8% 1/36 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	0.00% 0/35 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified	0.00% 0/36 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.	2.9% 1/35 • Number of events 1 • Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.

Additional Information

Lindell Weaver, MD, FACP, UHM

Intermountain Healthcare

Phone: 801-408-3623

Email: lindell.weaver@imail.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place