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

NCT02911688 | Completed Phase 2 Results

• 2 other identifiers: 15-19384R01ES023349-04
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

To study the effects of 1200mg gamma tocopherol, a form of vitamin E, given daily on the response of the airway in mild asthmatics after exposure to ozone (O3)

Conditions

Allergic Asthma

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Sputum Percent Neutrophils (%PMN) Following Ozone Exposure

  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.

  baseline and 6 hours post-ozone exposure

Secondary Outcomes (7)

• Change in Sputum Percent Eosinophils From Baseline Following Ozone Exposure

  baseline and 6 hours post-ozone exposure

• Change in Sputum Interleukin (IL)-1b From Baseline Following Ozone Exposure

  baseline and 6 hours post ozone exposure

• Change in Sputum IL-6 From Baseline Following Ozone Exposure

  baseline and 6 hours post ozone exposure

• Change in Sputum IL-8 From Baseline Following Ozone Exposure

  baseline and 6 hours post ozone exposure

• Change in Sputum Tumor Necrosis Factor (TNF)-Alpha From Baseline Following Ozone Exposure

  baseline and 6 hours post ozone exposure

Study Arms (2)

placebo

PLACEBO COMPARATOR

Safflower oil, taken in 2 capsules every 12 hours for a total of 4 doses

Drug: Placebo

gamma tocopherol

ACTIVE COMPARATOR

gamma tocopherol 1400 mg, taken as 2 700 mg capsules every 12 hours for a total of 4 doses

Drug: gamma tocopherol

Interventions

gamma tocopherol DRUG

The effect of supplemental with gamma tocopherol on O3 response will be assessed using the difference pre and after γT dosing.

Also known as: Vitamin E

gamma tocopherol

Placebo DRUG

The effect of supplemental with gamma tocopherol on O3 response will be assessed using the difference pre and after placebo dosing.

Also known as: Safflower oil

placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-45 of both genders
• Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy
• History of episodic wheezing, chest tightness, or shortness of breath consistent with asthma, or physician diagnosed asthma.
• Positive methacholine test. A positive test is defined as a provocative concentration of methacholine of 10 mg/ml or less producing a 15% fall in forced expiratory volume in 1 second (FEV1) (PC20 methacholine) by the method used in a separate screening protocol or a pre and post bronchodilator challenge used to determine reversible lung function. Reversibility is confirmed with a 10-12% increase in FEV1 15 minutes after inhaling 4 puffs of albuterol with a spacer. Reversibility is used in the same separate screening protocol; or a clinical history of asthma after the age of 6.
• FEV1 of at least 80% of predicted and FEV1/Forced Vital Capacity (FVC) ratio of at least .70 (without use of bronchodilating medications for 12 hours or long acting beta agonists for 24 hours), consistent with lung function of persons with no more than mild episodic or mild persistent asthma.
• Allergic sensitization to at least one of the following allergen preparations: (House Dust Mite f, House dust mite p, Cockroach, Tree mix, Grass Mix, Weed Mix, Mold Mix 1, Mold Mix 2, Rat, Mouse, Guinea Pig, Rabbit, Cat or Dog) confirmed by positive immediate skin test response; or a clinical history consistent with seasonal or perennial allergy symptoms.
• Symptom Score (this will be submitted as an attachment) no greater than 20 (out of a possible 60) for total symptom score with a value no greater than 3 for any one score. No more than one score may be greater or equal than 3.
• subjects must be willing to avoid caffeine for 12 hours prior to all visits. Methacholine challenge and allergy skin testing are performed as part of IRB 98-0799, which a subject must complete in order to be considered for this protocol.
• for subjects who are prescribed inhaled corticosteroids (ICS). These volunteers must be able to come off of the ICS for 2 weeks without increased symptoms or increased need for beta agonist rescue medication prior to screening and throughout the course of the study.

You may not qualify if:

• Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes, chronic renal disease, chronic thyroid disease, history of chronic infections/immunodeficiency, history of tuberculosis
• Physician directed emergency treatment for an asthma exacerbation within the preceding 3 months
• Moderate or Severe asthma
• Exacerbation of asthma more than 2x/week which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
• Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma. (Not to include prophylactic use of albuterol prior to exercise).
• Viral upper respiratory tract infection within 4 weeks of challenge.
• Any acute infection requiring antibiotics within 4 weeks of exposure or fever of unknown origin within 4 weeks of challenge.
• Severe asthma
• Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
• Medications which may impact the results of the O3 exposure, interfere with any other medications potentially used in the study (to include systemic steroids, beta antagonists, non-steroidal anti-inflammatory agents)
• Any history of smoking in the year prior to study enrollment; lifetime smoking history \> 10 pack years
• Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma
• Allergy/sensitivity to study drugs, or their formulations.
• Known hypersensitivity to methacholine or to other parasympathomimetic agents
• History of intubation for asthma

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Environmental Health Sciences (NIEHS): collaborator

Study Sites (1)

Center for Environmental Medicine, Asthma and Lung Biology

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Interventions

gamma-Tocopherol; Vitamin E; Safflower Oil

Intervention Hierarchy (Ancestors)

Tocopherols; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fats, Unsaturated; Plant Oils; Oils; Plant Preparations; Biological Products; Complex Mixtures; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Results Point of Contact

• Title: Carole Robinette Assistant Director of Clinical Research
• Organization: Center for Environmental Medicine Asthma and Lung Biology

carole_robinette@med.unc.edu

919 966-5638

Study Officials

• David B Peden, MD

  UNC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2016
• First Posted: September 22, 2016
• Study Start: September 1, 2016
• Primary Completion: February 13, 2019
• Study Completion: February 13, 2019
• Last Updated: January 18, 2020
• Results First Posted: January 18, 2020

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)