Trial Outcomes & Findings for Effect of Gamma Tocopherol Enriched Supplementation on Response to Inhaled O3 Exposure (NCT NCT02911688)

NCT ID: NCT02911688

Last Updated: 2020-01-18

Results Overview

Participants provide induced sputum samples before and 6 hours after Ozone exposure for measurements of inflammatory cells. The analysis will determine if gamma tocopherol pre-treatment reduces ozone-induced sputum percent neutrophils compared to placebo pre-treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 18 participants
• Primary outcome timeframe: baseline and 6 hours post-ozone exposure
• Results posted on: 2020-01-18

Participant Flow

Volunteers were screened for eligibility between September 2016 and November 2018 at the Center for Environmental Medicine, Asthma and Lung Biology at the University of North Carolina at Chapel Hill.

18 volunteers were randomized

Participant milestones

Measure	Placebo Then Gamma T Participants first received safflower oil, taken in two 700 mg capsules every 12 hours for a total of 4 doses followed by a washout period of at least 3 weeks. Then they received gamma tocopherol-enriched supplement taken in two 700 mg capsules (total of 1200 mg of gamma tocopherol) every 12 hours for a total of 4 doses.	Gamma Tocopherol Then Placebo Participants first received gamma tocopherol-enriched supplement taken in two 700 mg capsules (total of 1200 mg of gamma tocopherol) every 12 hours for a total of 4 doses, followed by a washout period of at least 3 weeks. They then received safflower oil, taken in two 700 mg capsules every 12 hours for a total of 4 doses.
First Intervention STARTED	9	9
First Intervention Received Intervention	9	9
First Intervention COMPLETED	9	9
First Intervention NOT COMPLETED	0	0
Washout STARTED	9	9
Washout COMPLETED	8	7
Washout NOT COMPLETED	1	2
Second Intervention STARTED	8	7
Second Intervention COMPLETED	8	7
Second Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Placebo Then Gamma T Participants first received safflower oil, taken in two 700 mg capsules every 12 hours for a total of 4 doses followed by a washout period of at least 3 weeks. Then they received gamma tocopherol-enriched supplement taken in two 700 mg capsules (total of 1200 mg of gamma tocopherol) every 12 hours for a total of 4 doses.	Gamma Tocopherol Then Placebo Participants first received gamma tocopherol-enriched supplement taken in two 700 mg capsules (total of 1200 mg of gamma tocopherol) every 12 hours for a total of 4 doses, followed by a washout period of at least 3 weeks. They then received safflower oil, taken in two 700 mg capsules every 12 hours for a total of 4 doses.
Washout Lost to Follow-up	1	1
Washout Withdrawal by Subject	0	1

Baseline Characteristics

Effect of Gamma Tocopherol Enriched Supplementation on Response to Inhaled O3 Exposure

Baseline characteristics by cohort

Measure	Placebo Then Gamma T n=9 Participants Safflower oil, taken in 2 capsules every 12 hours for a total of 4 doses followed by a washout period of at least 3 weeks and then gamma tocopherol will be taken as 2 gel tabs (1200 mg/dose) every 12 hours for a total of 4 doses.	Gamma Tocopherol Then Placebo n=9 Participants Gamma tocopherol will be taken 2 gel tabs (1200 mg/dose) every 12 hours for a total of 4 doses followed by a washout period of at least 3 weeks followed by safflower oil, taken in 2 capsules every 12 hours for a total of 4 doses.	Total n=18 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=93 Participants	9 Participants n=4 Participants	18 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Female	8 Participants n=93 Participants	5 Participants n=4 Participants	13 Participants n=27 Participants
Sex: Female, Male Male	1 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=93 Participants	9 Participants n=4 Participants	17 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) White	6 Participants n=93 Participants	8 Participants n=4 Participants	14 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	9 Participants n=93 Participants	9 Participants n=4 Participants	18 Participants n=27 Participants

PRIMARY outcome

Timeframe: baseline and 6 hours post-ozone exposure

Population: Due to variability in quality of induced sputum samples, paired assessments of pre and post-ozone sputum endpoints were limited to 7 volunteers.

Participants provide induced sputum samples before and 6 hours after Ozone exposure for measurements of inflammatory cells. The analysis will determine if gamma tocopherol pre-treatment reduces ozone-induced sputum percent neutrophils compared to placebo pre-treatment.

Outcome measures

Measure	Gamma Tocopherol (N=7) n=7 Participants gamma tocopherol 1400 mg, taken as two 700 mg capsules every 12 hours for a total of 4 doses	Placebo (N=7) n=7 Participants Safflower oil, taken in 2 capsules every 12 hours for a total of 4 doses
Change From Baseline in Sputum Percent Neutrophils (%PMN) Following Ozone Exposure	34.1 percent neutrophils Standard Deviation 20.2	36.5 percent neutrophils Standard Deviation 20.2

SECONDARY outcome

Timeframe: baseline and 6 hours post-ozone exposure

Population: Due to variability in quality of induced sputum samples, paired assessments of pre and post-ozone sputum endpoints were limited to 7 volunteers.

The investigators assessed induced sputum cellularity at baseline and 6 hours after ozone exposure to determine if treatment with gamma tocopherol/placebo impacts ozone-induced sputum eosinophilia.

Outcome measures

Measure	Gamma Tocopherol (N=7) n=7 Participants gamma tocopherol 1400 mg, taken as two 700 mg capsules every 12 hours for a total of 4 doses	Placebo (N=7) n=7 Participants Safflower oil, taken in 2 capsules every 12 hours for a total of 4 doses
Change in Sputum Percent Eosinophils From Baseline Following Ozone Exposure	0.8 percent eosinophils Standard Deviation 3.7	-1.1 percent eosinophils Standard Deviation 3.0

SECONDARY outcome

Timeframe: baseline and 6 hours post ozone exposure

Population: Sufficient paired sputum supernatants from pre and post-ozone were available for analysis from 15 volunteers.

Participants provide induced sputum samples before and 6 hours after Ozone exposure for measurements of inflammatory cytokines. The analysis will determine if gamma tocopherol pre-treatment reduces ozone-induced sputum inflammatory cytokine production compared to placebo pre-treatment.

Outcome measures

Measure	Gamma Tocopherol (N=7) n=15 Participants gamma tocopherol 1400 mg, taken as two 700 mg capsules every 12 hours for a total of 4 doses	Placebo (N=7) n=15 Participants Safflower oil, taken in 2 capsules every 12 hours for a total of 4 doses
Change in Sputum Interleukin (IL)-1b From Baseline Following Ozone Exposure	-9.7 picograms per milliliter Standard Deviation 65.9	176 picograms per milliliter Standard Deviation 687

SECONDARY outcome

Timeframe: baseline and 6 hours post ozone exposure

Population: Sufficient paired sputum supernatants from pre and post-ozone were available for analysis from 15 volunteers.

Participants provide induced sputum samples before and 6 hours after Ozone exposure for measurements of inflammatory cytokines. The analysis will determine if gamma tocopherol pre-treatment reduces ozone-induced sputum inflammatory cytokine production compared to placebo pre-treatment.

Outcome measures

Measure	Gamma Tocopherol (N=7) n=15 Participants gamma tocopherol 1400 mg, taken as two 700 mg capsules every 12 hours for a total of 4 doses	Placebo (N=7) n=15 Participants Safflower oil, taken in 2 capsules every 12 hours for a total of 4 doses
Change in Sputum IL-6 From Baseline Following Ozone Exposure	58.0 picograms per milliliter Standard Deviation 225.5	44.3 picograms per milliliter Standard Deviation 128.3

SECONDARY outcome

Timeframe: baseline and 6 hours post ozone exposure

Population: Sufficient paired sputum supernatants from pre and post-ozone were available for analysis from 12 volunteers.

Participants provide induced sputum samples before and 6 hours after Ozone exposure for measurements of inflammatory cytokines. The analysis will determine if gamma tocopherol pre-treatment reduces ozone-induced sputum inflammatory cytokine production compared to placebo pre-treatment.

Outcome measures

Measure	Gamma Tocopherol (N=7) n=12 Participants gamma tocopherol 1400 mg, taken as two 700 mg capsules every 12 hours for a total of 4 doses	Placebo (N=7) n=12 Participants Safflower oil, taken in 2 capsules every 12 hours for a total of 4 doses
Change in Sputum IL-8 From Baseline Following Ozone Exposure	-341.1 picograms per milliliter Standard Deviation 3027	406.8 picograms per milliliter Standard Deviation 2769

SECONDARY outcome

Timeframe: baseline and 6 hours post ozone exposure

Population: Sufficient paired sputum supernatants from pre and post-ozone were available for analysis from 13 volunteers.

Participants provide induced sputum samples before and 6 hours after Ozone exposure for measurements of inflammatory cytokines. The analysis will determine if gamma tocopherol pre-treatment reduces ozone-induced sputum inflammatory cytokine production compared to placebo pre-treatment.

Outcome measures

Measure	Gamma Tocopherol (N=7) n=13 Participants gamma tocopherol 1400 mg, taken as two 700 mg capsules every 12 hours for a total of 4 doses	Placebo (N=7) n=13 Participants Safflower oil, taken in 2 capsules every 12 hours for a total of 4 doses
Change in Sputum Tumor Necrosis Factor (TNF)-Alpha From Baseline Following Ozone Exposure	-61.1 picograms per milliliter Standard Deviation 179.1	-301.4 picograms per milliliter Standard Deviation 1090

SECONDARY outcome

Timeframe: baseline and 6 hours post ozone exposure

Population: Due to improper processing of the sputum samples, analysis of mucins could not be performed.

Participants provide induced sputum samples before and 6 hours after Ozone exposure for measurements of sputum mucins to determine if gamma tocopherol pre-treatment reduces ozone-induced sputum mucins compared to placebo pre-treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and 1 hour after exiting ozone chamber

Population: This population includes those participants who completed both arms of the study (paired assessments of MCC). One participant could not complete the whole lung clearance scan during one of the study periods and was excluded from the analysis.

Whole lung clearance was measured using gamma scintigraphy and represented as mean average 120 minute clearance of inhaled technetium (99mTc) sulfur colloid particles in order to estimate the rate of airway mucociliary clearance.

Outcome measures

Measure	Gamma Tocopherol (N=7) n=14 Participants gamma tocopherol 1400 mg, taken as two 700 mg capsules every 12 hours for a total of 4 doses	Placebo (N=7) n=14 Participants Safflower oil, taken in 2 capsules every 12 hours for a total of 4 doses
Change in Whole Lung Clearance of Technetium Sulfur Colloid Particles (0-120 Minutes) From Baseline Following Ozone Exposure	2 % clearance Standard Deviation 7	0 % clearance Standard Deviation 7

POST_HOC outcome

Timeframe: baseline and 1 hour after exiting ozone chamber

Population: This population includes those participants who completed both arms of the study (paired assessments of MCC). One participant could not complete the whole lung clearance scan during one of the study periods and was excluded from the analysis.

Central lung clearance (0-30 minutes) was measured using gamma scintigraphy and represented as mean average 30 minute clearance of inhaled technetium (99mTc) sulfur colloid particles from the large bronchial airways.

Outcome measures

Measure	Gamma Tocopherol (N=7) n=14 Participants gamma tocopherol 1400 mg, taken as two 700 mg capsules every 12 hours for a total of 4 doses	Placebo (N=7) n=14 Participants Safflower oil, taken in 2 capsules every 12 hours for a total of 4 doses
Change in Central Lung Clearance of Technetium Sulfur Colloid Particles (0-30 Minutes) From Baseline Following Ozone Exposure	-0.2 % clearance Standard Deviation 8.3	-4.3 % clearance Standard Deviation 5.0

Adverse Events

Gamma Tocopherol

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Gamma Tocopherol n=17 participants at risk gamma tocopherol 1400 mg, taken as 2 700 mg capsules every 12 hours for a total of 4 doses	Placebo n=16 participants at risk Safflower oil, taken in 2 capsules every 12 hours for a total of 4 doses
Gastrointestinal disorders GI Distress	29.4% 5/17 • Number of events 6 • Adverse event data was collected from the time of enrollment until the final study visit, occurring 5-10 days after the final ozone exposure (approximately 3 months and up to 6 months). If adverse events were reported at the final study visit, the participant was followed until resolution of the event. Participants completed a standardized symptom questionnaire before ozone exposure and again at 6 and 24 hours after ozone exposure. They also completed a standardized symptom questionnaire each day while taking study treatment. Participants also had the opportunity to self-report adverse events.	6.2% 1/16 • Number of events 1 • Adverse event data was collected from the time of enrollment until the final study visit, occurring 5-10 days after the final ozone exposure (approximately 3 months and up to 6 months). If adverse events were reported at the final study visit, the participant was followed until resolution of the event. Participants completed a standardized symptom questionnaire before ozone exposure and again at 6 and 24 hours after ozone exposure. They also completed a standardized symptom questionnaire each day while taking study treatment. Participants also had the opportunity to self-report adverse events.
General disorders nasal soreness	5.9% 1/17 • Number of events 1 • Adverse event data was collected from the time of enrollment until the final study visit, occurring 5-10 days after the final ozone exposure (approximately 3 months and up to 6 months). If adverse events were reported at the final study visit, the participant was followed until resolution of the event. Participants completed a standardized symptom questionnaire before ozone exposure and again at 6 and 24 hours after ozone exposure. They also completed a standardized symptom questionnaire each day while taking study treatment. Participants also had the opportunity to self-report adverse events.	0.00% 0/16 • Adverse event data was collected from the time of enrollment until the final study visit, occurring 5-10 days after the final ozone exposure (approximately 3 months and up to 6 months). If adverse events were reported at the final study visit, the participant was followed until resolution of the event. Participants completed a standardized symptom questionnaire before ozone exposure and again at 6 and 24 hours after ozone exposure. They also completed a standardized symptom questionnaire each day while taking study treatment. Participants also had the opportunity to self-report adverse events.
Respiratory, thoracic and mediastinal disorders URI	5.9% 1/17 • Number of events 1 • Adverse event data was collected from the time of enrollment until the final study visit, occurring 5-10 days after the final ozone exposure (approximately 3 months and up to 6 months). If adverse events were reported at the final study visit, the participant was followed until resolution of the event. Participants completed a standardized symptom questionnaire before ozone exposure and again at 6 and 24 hours after ozone exposure. They also completed a standardized symptom questionnaire each day while taking study treatment. Participants also had the opportunity to self-report adverse events.	6.2% 1/16 • Number of events 1 • Adverse event data was collected from the time of enrollment until the final study visit, occurring 5-10 days after the final ozone exposure (approximately 3 months and up to 6 months). If adverse events were reported at the final study visit, the participant was followed until resolution of the event. Participants completed a standardized symptom questionnaire before ozone exposure and again at 6 and 24 hours after ozone exposure. They also completed a standardized symptom questionnaire each day while taking study treatment. Participants also had the opportunity to self-report adverse events.
Respiratory, thoracic and mediastinal disorders Pain on deep inspiration	11.8% 2/17 • Number of events 2 • Adverse event data was collected from the time of enrollment until the final study visit, occurring 5-10 days after the final ozone exposure (approximately 3 months and up to 6 months). If adverse events were reported at the final study visit, the participant was followed until resolution of the event. Participants completed a standardized symptom questionnaire before ozone exposure and again at 6 and 24 hours after ozone exposure. They also completed a standardized symptom questionnaire each day while taking study treatment. Participants also had the opportunity to self-report adverse events.	0.00% 0/16 • Adverse event data was collected from the time of enrollment until the final study visit, occurring 5-10 days after the final ozone exposure (approximately 3 months and up to 6 months). If adverse events were reported at the final study visit, the participant was followed until resolution of the event. Participants completed a standardized symptom questionnaire before ozone exposure and again at 6 and 24 hours after ozone exposure. They also completed a standardized symptom questionnaire each day while taking study treatment. Participants also had the opportunity to self-report adverse events.
General disorders headache	0.00% 0/17 • Adverse event data was collected from the time of enrollment until the final study visit, occurring 5-10 days after the final ozone exposure (approximately 3 months and up to 6 months). If adverse events were reported at the final study visit, the participant was followed until resolution of the event. Participants completed a standardized symptom questionnaire before ozone exposure and again at 6 and 24 hours after ozone exposure. They also completed a standardized symptom questionnaire each day while taking study treatment. Participants also had the opportunity to self-report adverse events.	6.2% 1/16 • Number of events 1 • Adverse event data was collected from the time of enrollment until the final study visit, occurring 5-10 days after the final ozone exposure (approximately 3 months and up to 6 months). If adverse events were reported at the final study visit, the participant was followed until resolution of the event. Participants completed a standardized symptom questionnaire before ozone exposure and again at 6 and 24 hours after ozone exposure. They also completed a standardized symptom questionnaire each day while taking study treatment. Participants also had the opportunity to self-report adverse events.
Respiratory, thoracic and mediastinal disorders Shortness of Breath	5.9% 1/17 • Number of events 1 • Adverse event data was collected from the time of enrollment until the final study visit, occurring 5-10 days after the final ozone exposure (approximately 3 months and up to 6 months). If adverse events were reported at the final study visit, the participant was followed until resolution of the event. Participants completed a standardized symptom questionnaire before ozone exposure and again at 6 and 24 hours after ozone exposure. They also completed a standardized symptom questionnaire each day while taking study treatment. Participants also had the opportunity to self-report adverse events.	0.00% 0/16 • Adverse event data was collected from the time of enrollment until the final study visit, occurring 5-10 days after the final ozone exposure (approximately 3 months and up to 6 months). If adverse events were reported at the final study visit, the participant was followed until resolution of the event. Participants completed a standardized symptom questionnaire before ozone exposure and again at 6 and 24 hours after ozone exposure. They also completed a standardized symptom questionnaire each day while taking study treatment. Participants also had the opportunity to self-report adverse events.
Respiratory, thoracic and mediastinal disorders Wheezing	5.9% 1/17 • Number of events 1 • Adverse event data was collected from the time of enrollment until the final study visit, occurring 5-10 days after the final ozone exposure (approximately 3 months and up to 6 months). If adverse events were reported at the final study visit, the participant was followed until resolution of the event. Participants completed a standardized symptom questionnaire before ozone exposure and again at 6 and 24 hours after ozone exposure. They also completed a standardized symptom questionnaire each day while taking study treatment. Participants also had the opportunity to self-report adverse events.	0.00% 0/16 • Adverse event data was collected from the time of enrollment until the final study visit, occurring 5-10 days after the final ozone exposure (approximately 3 months and up to 6 months). If adverse events were reported at the final study visit, the participant was followed until resolution of the event. Participants completed a standardized symptom questionnaire before ozone exposure and again at 6 and 24 hours after ozone exposure. They also completed a standardized symptom questionnaire each day while taking study treatment. Participants also had the opportunity to self-report adverse events.

Additional Information

Carole Robinette Assistant Director of Clinical Research

Center for Environmental Medicine Asthma and Lung Biology

Phone: 919 966-5638

Email: carole_robinette@med.unc.edu

Results disclosure agreements

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