Trial Outcomes & Findings for Biopsychosocial Influence on Shoulder Pain (NCT NCT02620579)

NCT ID: NCT02620579

Last Updated: 2023-01-13

Results Overview

The outcome has a range between 0 and 1, the higher scores mean a better outcome. Successful recovery was determined based on meeting the recovery criterion for shoulder pain intensity by at least 6 days. Specifically, recovery (Yes or No) was defined using Brief Pain Inventory (BPI) ratings as a current pain intensity rating of 0/10 and a worst pain intensity rating of less than 2/10.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

264 participants

Primary outcome timeframe

Approximately 6 days

Results posted on

2023-01-13

Participant Flow

Periodic screenings of volunteers were completed on the University of Florida campus and in the local community. All participants provided informed consent to screening. Participants who screened as being in the high-risk subgroup and appropriate for exercise-induced muscle injury were eligible for participation in the clinical trial and provided additional informed consent.

Participants who were eligible based on being in the high-risk subgroup and appropriate for exercise-induced muscle injury were required to take additional testing to determine the appropriateness of receiving propranolol and also identifying other medical reasons for exclusion. 3 enrolled participants were excluded/withdrawn pre-randomization.

Participant milestones

Participant milestones
Measure	Personalized Pharmaceutical and Education (C) This group will have propranolol (Propranolol LA) 60 mg administered orally and receive the pain processing education modules as the combined intervention for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, General Education (B) This group will have the placebo pharmaceutical administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, Personalized Education (A) This group will have the placebo pharmaceutical administered orally and receive the pain processing education modules as the combined intervention for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Personalized Pharmaceutical, General Education (D) This group will have propranolol (Propranolol LA) 60 mg administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.
Overall Study STARTED	62	57	57	57
Overall Study COMPLETED	62	56	56	56
Overall Study NOT COMPLETED	0	1	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Personalized Pharmaceutical and Education (C) This group will have propranolol (Propranolol LA) 60 mg administered orally and receive the pain processing education modules as the combined intervention for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, General Education (B) This group will have the placebo pharmaceutical administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, Personalized Education (A) This group will have the placebo pharmaceutical administered orally and receive the pain processing education modules as the combined intervention for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Personalized Pharmaceutical, General Education (D) This group will have propranolol (Propranolol LA) 60 mg administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.
Overall Study Physician Decision	0	0	0	1
Overall Study Withdrawal by Subject	0	1	1	0

Baseline Characteristics

Biopsychosocial Influence on Shoulder Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Personalized Pharmaceutical and Education (C) n=62 Participants This group will have propranolol (Propranolol LA) 60 mg administered orally and receive the pain processing education modules as the combined intervention for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, General Education (B) n=57 Participants This group will have the placebo pharmaceutical administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, Personalized Education (A) n=57 Participants This group will have the placebo pharmaceutical administered orally and receive the pain processing education modules as the combined intervention for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Personalized Pharmaceutical, General Education (D) n=57 Participants This group will have propranolol (Propranolol LA) 60 mg administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Total n=233 Participants Total of all reporting groups
Age, Continuous	21.4 years STANDARD_DEVIATION 5.3 • n=5 Participants	20.3 years STANDARD_DEVIATION 2.5 • n=7 Participants	21.7 years STANDARD_DEVIATION 5.9 • n=5 Participants	20.5 years STANDARD_DEVIATION 1.9 • n=4 Participants	21.0 years STANDARD_DEVIATION 4.3 • n=21 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	37 Participants n=7 Participants	39 Participants n=5 Participants	37 Participants n=4 Participants	153 Participants n=21 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	20 Participants n=7 Participants	18 Participants n=5 Participants	20 Participants n=4 Participants	80 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	23 Participants n=5 Participants	14 Participants n=7 Participants	19 Participants n=5 Participants	21 Participants n=4 Participants	77 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	39 Participants n=5 Participants	43 Participants n=7 Participants	38 Participants n=5 Participants	36 Participants n=4 Participants	156 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	15 Participants n=5 Participants	20 Participants n=7 Participants	18 Participants n=5 Participants	18 Participants n=4 Participants	71 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	15 Participants n=7 Participants	13 Participants n=5 Participants	7 Participants n=4 Participants	45 Participants n=21 Participants
Race (NIH/OMB) White	33 Participants n=5 Participants	20 Participants n=7 Participants	24 Participants n=5 Participants	31 Participants n=4 Participants	108 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	7 Participants n=21 Participants
Region of Enrollment United States	62 Participants n=5 Participants	57 Participants n=7 Participants	57 Participants n=5 Participants	57 Participants n=4 Participants	233 Participants n=21 Participants
Body Mass Index (BMI)	23.6 kg/m^2 STANDARD_DEVIATION 4.4 • n=5 Participants	23.9 kg/m^2 STANDARD_DEVIATION 4.1 • n=7 Participants	24.1 kg/m^2 STANDARD_DEVIATION 4.5 • n=5 Participants	23.4 kg/m^2 STANDARD_DEVIATION 4.3 • n=4 Participants	23.7 kg/m^2 STANDARD_DEVIATION 4.3 • n=21 Participants
Fear of Pain Questionnaire (FPQ)	14.5 units on a scale STANDARD_DEVIATION 6.0 • n=5 Participants	14.6 units on a scale STANDARD_DEVIATION 7.0 • n=7 Participants	15.6 units on a scale STANDARD_DEVIATION 6.8 • n=5 Participants	14.5 units on a scale STANDARD_DEVIATION 5.5 • n=4 Participants	14.8 units on a scale STANDARD_DEVIATION 6.3 • n=21 Participants
Pain Catastrophizing Scale (PCS)	12.6 units on a scale STANDARD_DEVIATION 9.1 • n=5 Participants	12.6 units on a scale STANDARD_DEVIATION 7.2 • n=7 Participants	12.7 units on a scale STANDARD_DEVIATION 9.0 • n=5 Participants	11.4 units on a scale STANDARD_DEVIATION 7.8 • n=4 Participants	12.3 units on a scale STANDARD_DEVIATION 8.3 • n=21 Participants
Patient Health Questionnaire-9 (PHQ-9)	1.9 units on a scale STANDARD_DEVIATION 2.3 • n=5 Participants	2.8 units on a scale STANDARD_DEVIATION 3.1 • n=7 Participants	3.2 units on a scale STANDARD_DEVIATION 4.4 • n=5 Participants	2.9 units on a scale STANDARD_DEVIATION 3.8 • n=4 Participants	2.7 units on a scale STANDARD_DEVIATION 3.5 • n=21 Participants
Tampa Scale for Kinesiophobia-11 (TSK-11)	19.6 units on a scale STANDARD_DEVIATION 4.7 • n=5 Participants	19.5 units on a scale STANDARD_DEVIATION 5.0 • n=7 Participants	19.4 units on a scale STANDARD_DEVIATION 5.7 • n=5 Participants	19.8 units on a scale STANDARD_DEVIATION 5.2 • n=4 Participants	19.5 units on a scale STANDARD_DEVIATION 5.1 • n=21 Participants

PRIMARY outcome

Timeframe: Approximately 6 days

Population: Analysis Population consists of 233 participants. 28 out of 261 randomized participants were excluded due to criteria related to the safety of propranolol administration (eg, abnormal ECG findings) or a candidate not being able to complete the study (eg, change in time commitment). These post-randomization exclusions were made for safety reasons and participants were excluded prior to any baseline data collection, induction of exercise-induced muscle injury, and treatment allocation.

Outcome measures

Outcome measures
Measure	Personalized Pharmaceutical and Education (C) n=62 Participants This group will have propranolol (Propranolol LA) 60 mg administered orally and receive the pain processing education modules as the combined intervention for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, General Education (B) n=57 Participants This group will have the placebo pharmaceutical administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, Personalized Education (A) n=57 Participants This group will have the placebo pharmaceutical administered orally and receive the pain processing education modules as the combined intervention for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Personalized Pharmaceutical, General Education (D) n=57 Participants This group will have propranolol (Propranolol LA) 60 mg administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.
Number of Participants Who Met the Recovery Criterion for Shoulder Pain Intensity	39 Participants	32 Participants	32 Participants	32 Participants

SECONDARY outcome

Timeframe: Daily until recovery criterion met, approximately 5-15 days

The Brief Pain Inventory (BPI) consists of rating pain intensity on an 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst pain intensity imaginable). BPI will be recorded daily and the recovery criterion used for this study will be a BPI rating of current pain 0/10 and worst pain rating of less than 2/10. The pain duration is number of days from the date of induced pain to date of recovery. The longer the duration means a worse outcome.

Outcome measures

Outcome measures
Measure	Personalized Pharmaceutical and Education (C) n=62 Participants This group will have propranolol (Propranolol LA) 60 mg administered orally and receive the pain processing education modules as the combined intervention for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, General Education (B) n=57 Participants This group will have the placebo pharmaceutical administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, Personalized Education (A) n=57 Participants This group will have the placebo pharmaceutical administered orally and receive the pain processing education modules as the combined intervention for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Personalized Pharmaceutical, General Education (D) n=57 Participants This group will have propranolol (Propranolol LA) 60 mg administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.
Brief Pain Inventory (BPI) for Pain Duration	4 days Interval 4.0 to 9.0	4 days Interval 1.0 to 11.0	4 days Interval 0.0 to 11.0	4 days Interval 4.0 to 9.0

SECONDARY outcome

Timeframe: Day 2 value of the worst pain intensity is reported

The Brief Pain Inventory (BPI) which consists of rating pain intensity on an 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst pain intensity imaginable). Participants will rate their current, best, and worst pain intensity on the BPI. This measure will be recorded daily through study completion, an average of 5 days. The worst pain intensity rating at Day 2 (when participants usually had the Peak Shoulder Pain Intensity) is reported.

Outcome measures

Outcome measures
Measure	Personalized Pharmaceutical and Education (C) n=62 Participants This group will have propranolol (Propranolol LA) 60 mg administered orally and receive the pain processing education modules as the combined intervention for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, General Education (B) n=57 Participants This group will have the placebo pharmaceutical administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, Personalized Education (A) n=57 Participants This group will have the placebo pharmaceutical administered orally and receive the pain processing education modules as the combined intervention for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Personalized Pharmaceutical, General Education (D) n=57 Participants This group will have propranolol (Propranolol LA) 60 mg administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.
Brief Pain Inventory (BPI) for Worst Shoulder Pain Intensity (Highest Daily Pain Intensity Rating) Recorded During Recovery.	2.9 score on a scale Standard Deviation 1.9	3.2 score on a scale Standard Deviation 2.1	2.9 score on a scale Standard Deviation 2.1	3.1 score on a scale Standard Deviation 2.0

SECONDARY outcome

Timeframe: Daily until recovery criterion met, approximately 5-15 days

The abridged version of the DASH (the QuickDASH) which consists of 11 functional items, with total scores ranging from 0 (not disability) to 100 (complete disability) will be used to assess upper-extremity disability. The primary outcome will be the highest DASH score recorded during the pain intensity recovery period.

Outcome measures

Outcome measures
Measure	Personalized Pharmaceutical and Education (C) n=62 Participants This group will have propranolol (Propranolol LA) 60 mg administered orally and receive the pain processing education modules as the combined intervention for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, General Education (B) n=57 Participants This group will have the placebo pharmaceutical administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, Personalized Education (A) n=57 Participants This group will have the placebo pharmaceutical administered orally and receive the pain processing education modules as the combined intervention for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Personalized Pharmaceutical, General Education (D) n=57 Participants This group will have propranolol (Propranolol LA) 60 mg administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.
Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH)	8.2 score on a scale Standard Deviation 8.5	10.5 score on a scale Standard Deviation 12.4	11.4 score on a scale Standard Deviation 12.9	9.4 score on a scale Standard Deviation 8.3

Adverse Events

Personalized Pharmaceutical and Education (C)

Serious events: 0 serious events

Other events: 49 other events

Deaths: 0 deaths

Placebo Pharmaceutical, General Education (B)

Serious events: 0 serious events

Other events: 43 other events

Deaths: 0 deaths

Placebo Pharmaceutical, Personalized Education (A)

Serious events: 0 serious events

Other events: 39 other events

Deaths: 0 deaths

Personalized Pharmaceutical, General Education (D)

Serious events: 0 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Personalized Pharmaceutical and Education (C) n=62 participants at risk This group will have propranolol (Propranolol LA) 60 mg administered orally and receive the pain processing education modules as the combined intervention for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, General Education (B) n=57 participants at risk This group will have the placebo pharmaceutical administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Placebo Pharmaceutical, Personalized Education (A) n=57 participants at risk This group will have the placebo pharmaceutical administered orally and receive the pain processing education modules as the combined intervention for this arm. Placebo: Placebo capsules will be prepared by the University of Florida Investigational Drug Service to be visually indistinguishable from the active medication and delivered orally. Placebo administration will be done in the same fashion as propranolol - administered on Days 1 (before exercise induced muscle injury) and the Days 2-4 after the exercise induced muscle injury. Pain Processing Education: Pain processing education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of better understanding of pain processing and psycho-education. This information will encourage shoulder activation by: a) reducing the threat of muscle injury; b) encouraging normal use of the shoulder and arm; and c) addressing specific concerns expressed by the subject (e.g. pain with shoulder motion is a sign of re-injury). This education component will be devoid of detailed information on shoulder anatomy, movement, and injury that characterizes the Shoulder Anatomy Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.	Personalized Pharmaceutical, General Education (D) n=57 participants at risk This group will have propranolol (Propranolol LA) 60 mg administered orally and receive general shoulder anatomy education modules as the interventions for this arm. Propranolol LA (60 mg): Long-acting propranolol (Propranolol LA) 60 mg to be administered orally daily for Days 1 (before exercise induced muscle injury) and Days 2-4 following exercise induced muscle injury. Shoulder Anatomy Education: Shoulder anatomy education modules will be administered Days 2-4 (after exercised induced muscle injury) following exercise enhance injury with the goal of participant understanding shoulder anatomy and injury while reviewing: a) structure and arthrokinematics of the shoulder joint; b) muscle anatomy of the shoulder with emphasis on the rotator cuff; and c) potential shoulder pain generators from the exercise-induced injury. This education component will be devoid of information related to pain signaling and cognitive restructuring that characterizes Pain Processing Education modules. These education modules will be scripted and structured so they are provided in a standardized manner for all subjects.
General disorders Light headedness	27.4% 17/62 • Number of events 22 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	29.8% 17/57 • Number of events 28 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	31.6% 18/57 • Number of events 30 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	24.6% 14/57 • Number of events 17 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.
Blood and lymphatic system disorders Slowed heartbeat	3.2% 2/62 • Number of events 6 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	7.0% 4/57 • Number of events 4 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	7.0% 4/57 • Number of events 4 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	1.8% 1/57 • Number of events 1 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.
Musculoskeletal and connective tissue disorders Weakness	40.3% 25/62 • Number of events 44 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	42.1% 24/57 • Number of events 56 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	43.9% 25/57 • Number of events 51 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	33.3% 19/57 • Number of events 45 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.
Musculoskeletal and connective tissue disorders Fatigue	56.5% 35/62 • Number of events 67 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	52.6% 30/57 • Number of events 77 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	56.1% 32/57 • Number of events 87 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	63.2% 36/57 • Number of events 74 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.
Gastrointestinal disorders Gastrointestinal upset	16.1% 10/62 • Number of events 16 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	19.3% 11/57 • Number of events 18 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	21.1% 12/57 • Number of events 17 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	10.5% 6/57 • Number of events 8 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.
General disorders Allergic reactions	1.6% 1/62 • Number of events 2 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	0.00% 0/57 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	0.00% 0/57 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	1.8% 1/57 • Number of events 3 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.
General disorders Dizziness	9.7% 6/62 • Number of events 6 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	14.0% 8/57 • Number of events 10 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	14.0% 8/57 • Number of events 15 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	14.0% 8/57 • Number of events 11 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.
Gastrointestinal disorders Nausea/Vomiting	12.9% 8/62 • Number of events 8 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	12.3% 7/57 • Number of events 13 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	12.3% 7/57 • Number of events 12 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	8.8% 5/57 • Number of events 7 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.
Nervous system disorders Numbness/tingling in the hands	6.5% 4/62 • Number of events 4 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	10.5% 6/57 • Number of events 10 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	10.5% 6/57 • Number of events 9 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	7.0% 4/57 • Number of events 5 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.
General disorders Sleep problems	19.4% 12/62 • Number of events 21 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	33.3% 19/57 • Number of events 43 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	22.8% 13/57 • Number of events 26 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	24.6% 14/57 • Number of events 33 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.
General disorders Depression	3.2% 2/62 • Number of events 4 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	3.5% 2/57 • Number of events 4 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	3.5% 2/57 • Number of events 6 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.	1.8% 1/57 • Number of events 1 • 5 days Mortality and serious adverse events were monitored. Side effects were closely monitored and captured by self-report at the beginning of each study session (starting on day 2), thus reflecting the prior day response to the study drug.

Additional Information

Dr. Samuel S. Wu

University of Florida

Phone: 3522945910

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place