Trial Outcomes & Findings for Effect of Gamma Tocopherol Enriched Supplementation on Response to Inhaled LPS (NCT NCT02104505)
NCT ID: NCT02104505
Last Updated: 2017-11-06
Results Overview
In asthmatic individuals, exposure to CCRE is expected to increase PMNs in the sputum. The sputum PMNs were measured at baseline (immediately prior to dosing) and again on day 14 of treatment (approximately 8 hours after the final dose) with placebo or gamma tocopherol. The outcome is to compare the change in PMNs from baseline to post treatment after exposure to CCRE
COMPLETED
PHASE1/PHASE2
23 participants
after 14 days of gamma tocopherol or placebo treatment
2017-11-06
Participant Flow
There was no wash out or run-in phase prior to treatment assignment. No enrolled participants were excluded prior to treatment assignment.
Participant milestones
| Measure |
Gamma Tocopherol (14 Days) Then Placebo (14 Days)
Gamma Tocopherol (2 capsules, each containing 700 mg, daily) x 14 days, washout for minimum 3 weeks, then Safflower oil capsules x 14 days
|
Placebo (14 Days) Then Gamma Tocopherol (14 Days)
Safflower oil capsules x 14 days, washout for minimum 3 weeks, then Gamma Tocopherol (2 capsules, each containing 700 mg, daily) x 14 days
|
|---|---|---|
|
First Intervention (14 Days)
STARTED
|
12
|
11
|
|
First Intervention (14 Days)
COMPLETED
|
10
|
8
|
|
First Intervention (14 Days)
NOT COMPLETED
|
2
|
3
|
|
Washout (Minimum 3 Weeks)
STARTED
|
10
|
8
|
|
Washout (Minimum 3 Weeks)
COMPLETED
|
10
|
8
|
|
Washout (Minimum 3 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Second Intervention (14 Days)
STARTED
|
10
|
8
|
|
Second Intervention (14 Days)
COMPLETED
|
8
|
7
|
|
Second Intervention (14 Days)
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Gamma Tocopherol (14 Days) Then Placebo (14 Days)
Gamma Tocopherol (2 capsules, each containing 700 mg, daily) x 14 days, washout for minimum 3 weeks, then Safflower oil capsules x 14 days
|
Placebo (14 Days) Then Gamma Tocopherol (14 Days)
Safflower oil capsules x 14 days, washout for minimum 3 weeks, then Gamma Tocopherol (2 capsules, each containing 700 mg, daily) x 14 days
|
|---|---|---|
|
First Intervention (14 Days)
Adverse Event
|
2
|
0
|
|
First Intervention (14 Days)
Withdrawal by Subject
|
0
|
1
|
|
First Intervention (14 Days)
Lost to Follow-up
|
0
|
1
|
|
First Intervention (14 Days)
exclusionary condition
|
0
|
1
|
|
Second Intervention (14 Days)
Withdrawal by Subject
|
0
|
1
|
|
Second Intervention (14 Days)
Adverse Event
|
2
|
0
|
Baseline Characteristics
Effect of Gamma Tocopherol Enriched Supplementation on Response to Inhaled LPS
Baseline characteristics by cohort
| Measure |
Gamma Tocopherol (14 Days) Then Placebo (14 Days)
n=12 Participants
Gamma Tocopherol (2 capsules, each containing 700 mg, daily) x 14 days, washout for minimum 3 weeks, then Safflower oil capsules x 14 days
|
Placebo (14 Days) Then Gamma Tocopherol (14 Days)
n=11 Participants
Safflower oil capsules x 14 days, washout for minimum 3 weeks, then Gamma Tocopherol (2 capsules, each containing 700 mg, daily) x 14 days
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
23.5 years
n=5 Participants
|
30 years
n=7 Participants
|
26 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
22 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
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
12 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Atopy
|
9 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
27.1 kg/m2
n=5 Participants
|
25.2 kg/m2
n=7 Participants
|
26 kg/m2
n=5 Participants
|
|
Forced expiratory volume in 1 second (FEV1) (%predicted)
|
102.5 percent predicted
n=5 Participants
|
90 percent predicted
n=7 Participants
|
97 percent predicted
n=5 Participants
|
PRIMARY outcome
Timeframe: after 14 days of gamma tocopherol or placebo treatmentPopulation: Since this study employed a crossover design, only participants who completed both arms of the study were included in the analysis.
In asthmatic individuals, exposure to CCRE is expected to increase PMNs in the sputum. The sputum PMNs were measured at baseline (immediately prior to dosing) and again on day 14 of treatment (approximately 8 hours after the final dose) with placebo or gamma tocopherol. The outcome is to compare the change in PMNs from baseline to post treatment after exposure to CCRE
Outcome measures
| Measure |
Gamma Tocopherol
n=15 Participants
Gamma Tocopherol 700 mg capsules,: 2 capsules daily for 14 days
|
Placebo
n=15 Participants
700 mg Safflower oil capsules; 2 capsules daily for 14 days
|
|---|---|---|
|
Comparison of Change in Sputum Percent Neutrophils (PMN)s Following Inhaled Clinical Center Reference Endotoxin (CCRE) Challenge as Affected by Gamma Tocopherol
|
11.7 change in percentage of PMNs in sputum
Standard Deviation 20.7
|
20.1 change in percentage of PMNs in sputum
Standard Deviation 16.5
|
SECONDARY outcome
Timeframe: after 14 days of gamma tocopherol or placebo treatmentPopulation: Since this study employs a crossover design, only participants who completed both arms of the study were included in the final analysis.
The sputum eosinophils were measured at baseline (immediately prior to dosing) and again after 14 days of treatment (approximately 8 hours after the final dose) with placebo or gamma tocopherol. The outcome is to compare sputum eosinophils per mg before and after gamma tocopherol treatment.
Outcome measures
| Measure |
Gamma Tocopherol
n=15 Participants
Gamma Tocopherol 700 mg capsules,: 2 capsules daily for 14 days
|
Placebo
n=15 Participants
700 mg Safflower oil capsules; 2 capsules daily for 14 days
|
|---|---|---|
|
Chronic Eosinophilic Airway Inflammation as Affected by Gamma Tocopherol
|
2.6 eosinophils per mg sputum
Standard Deviation 4.3
|
9.5 eosinophils per mg sputum
Standard Deviation 14.3
|
SECONDARY outcome
Timeframe: after 14 days of gamma tocopherol or placebo treatmentPopulation: Due to the crossover design of the study, only participants who completed both arms of the study were included in the analysis.
On day 14 of treatment (approximately 6 hours after the final dose) with placebo or gamma tocopherol, a whole lung region of interest (ROI) bordering the right lung was used to estimate (by computer analysis) whole lung retention of inhaled radiolabeled particles. This was performed by measuring the labeled particle counts over a 2 hour period and determining the fraction of initial particle counts remaining. From this data, we determined the percentage of labeled particles cleared from the lung during the 2 hour observation period.
Outcome measures
| Measure |
Gamma Tocopherol
n=15 Participants
Gamma Tocopherol 700 mg capsules,: 2 capsules daily for 14 days
|
Placebo
n=15 Participants
700 mg Safflower oil capsules; 2 capsules daily for 14 days
|
|---|---|---|
|
Mucociliary Clearance (MCC) Associated With CCRE Challenge as Affected by Gamma Tocopherol
|
20.2 % of labeled particles cleared from lung
Standard Deviation 8
|
16.3 % of labeled particles cleared from lung
Standard Deviation 9.3
|
SECONDARY outcome
Timeframe: after 11 days of gamma tocopherol or placebo treatmentPopulation: Due to the crossover study design, only participants who completed both arms of the study were included in the analysis.
On day 11 of treatment (approximately 6 hours after the daily dose) with placebo or gamma tocopherol, a whole lung region of interest (ROI) bordering the right lung was used to estimate (by computer analysis) whole lung retention of inhaled radiolabeled particles. This was performed by measuring the labeled particle counts over a 2 hour period and determining the fraction of initial particle counts remaining. From this data, we determined the percentage of labeled particles cleared from the lung during the 2 hour observation period.
Outcome measures
| Measure |
Gamma Tocopherol
n=15 Participants
Gamma Tocopherol 700 mg capsules,: 2 capsules daily for 14 days
|
Placebo
n=15 Participants
700 mg Safflower oil capsules; 2 capsules daily for 14 days
|
|---|---|---|
|
Mucociliary Clearance as Affected by Gamma Tocopherol
|
21.4 % of labeled particles cleared from lung
Standard Deviation 9.7
|
21.4 % of labeled particles cleared from lung
Standard Deviation 6.9
|
Adverse Events
Gamma Tocopherol
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Gamma Tocopherol
n=17 participants at risk
Gamma Tocopherol 700 mg capsules; 2 capsules daily for 14 days
|
Placebo
n=20 participants at risk
700 mg Safflower oil capsules; 2 capsules daily for 14 days
|
|---|---|---|
|
Nervous system disorders
Headache
|
11.8%
2/17 • Number of events 2 • 3 months on average
|
5.0%
1/20 • Number of events 2 • 3 months on average
|
|
Respiratory, thoracic and mediastinal disorders
Cough during CCRE challenge
|
41.2%
7/17 • Number of events 7 • 3 months on average
|
30.0%
6/20 • Number of events 6 • 3 months on average
|
|
Gastrointestinal disorders
Diminished sense of taste
|
0.00%
0/17 • 3 months on average
|
5.0%
1/20 • Number of events 1 • 3 months on average
|
|
Skin and subcutaneous tissue disorders
Skin redness
|
0.00%
0/17 • 3 months on average
|
5.0%
1/20 • Number of events 1 • 3 months on average
|
|
Cardiac disorders
Vagal response
|
5.9%
1/17 • Number of events 1 • 3 months on average
|
0.00%
0/20 • 3 months on average
|
|
Gastrointestinal disorders
Nausea
|
35.3%
6/17 • Number of events 6 • 3 months on average
|
0.00%
0/20 • 3 months on average
|
|
Gastrointestinal disorders
Vomiting
|
5.9%
1/17 • Number of events 1 • 3 months on average
|
0.00%
0/20 • 3 months on average
|
|
Gastrointestinal disorders
Diarrhea
|
23.5%
4/17 • Number of events 4 • 3 months on average
|
5.0%
1/20 • Number of events 1 • 3 months on average
|
|
Gastrointestinal disorders
Abdominal bloating
|
11.8%
2/17 • Number of events 2 • 3 months on average
|
0.00%
0/20 • 3 months on average
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
5.9%
1/17 • Number of events 1 • 3 months on average
|
0.00%
0/20 • 3 months on average
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of breath
|
5.9%
1/17 • Number of events 1 • 3 months on average
|
0.00%
0/20 • 3 months on average
|
|
Respiratory, thoracic and mediastinal disorders
Cough during sputum induction
|
5.9%
1/17 • Number of events 1 • 3 months on average
|
0.00%
0/20 • 3 months on average
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of breath during sputum induction
|
0.00%
0/17 • 3 months on average
|
5.0%
1/20 • Number of events 1 • 3 months on average
|
|
Gastrointestinal disorders
Heartburn
|
0.00%
0/17 • 3 months on average
|
5.0%
1/20 • Number of events 1 • 3 months on average
|
|
Gastrointestinal disorders
Loose stools
|
5.9%
1/17 • Number of events 1 • 3 months on average
|
5.0%
1/20 • Number of events 1 • 3 months on average
|
|
Gastrointestinal disorders
Loss of appetite
|
5.9%
1/17 • Number of events 1 • 3 months on average
|
0.00%
0/20 • 3 months on average
|
|
Gastrointestinal disorders
Flatulence
|
5.9%
1/17 • Number of events 1 • 3 months on average
|
0.00%
0/20 • 3 months on average
|
|
Respiratory, thoracic and mediastinal disorders
Chest tightness
|
5.9%
1/17 • Number of events 1 • 3 months on average
|
5.0%
1/20 • Number of events 1 • 3 months on average
|
|
Renal and urinary disorders
Urinary tract infection
|
0.00%
0/17 • 3 months on average
|
5.0%
1/20 • Number of events 1 • 3 months on average
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/17 • 3 months on average
|
5.0%
1/20 • Number of events 1 • 3 months on average
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/17 • 3 months on average
|
5.0%
1/20 • Number of events 1 • 3 months on average
|
|
Gastrointestinal disorders
Stomach cramps
|
0.00%
0/17 • 3 months on average
|
5.0%
1/20 • Number of events 1 • 3 months on average
|
Additional Information
Allison Burbank, MD
Center for Environmental Medicine, Asthma and Lung Biology; University of North Carolina, Chapel Hill
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place