Effect of Gamma Tocopherol Enriched Supplementation on Response to Inhaled LPS

NCT02104505 | Completed Phase 1 Results

• 2 other identifiers: 13-1605R01ES023349
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

To test the hypothesis that gamma tocopherol (vitamin E) supplement inhibits endotoxin induced airways inflammation in allergic asthmatics

Conditions

Mild, Allergic Asthma

Outcome Measures

Primary Outcomes (1)

• Comparison of Change in Sputum Percent Neutrophils (PMN)s Following Inhaled Clinical Center Reference Endotoxin (CCRE) Challenge as Affected by Gamma Tocopherol

  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

  after 14 days of gamma tocopherol or placebo treatment

Secondary Outcomes (3)

• Chronic Eosinophilic Airway Inflammation as Affected by Gamma Tocopherol

  after 14 days of gamma tocopherol or placebo treatment

• Mucociliary Clearance (MCC) Associated With CCRE Challenge as Affected by Gamma Tocopherol

  after 14 days of gamma tocopherol or placebo treatment

• Mucociliary Clearance as Affected by Gamma Tocopherol

  after 11 days of gamma tocopherol or placebo treatment

Study Arms (2)

700 mg Gamma Tocopherol daily x 14days

ACTIVE COMPARATOR

Gamma Tocopherol supplement

Drug: Gamma Tocopherol 700 mg capsules,

Placebo

PLACEBO COMPARATOR

Safflower oil capsules

Drug: Placebo

Interventions

Gamma Tocopherol 700 mg capsules, DRUG

2 capsules daily

700 mg Gamma Tocopherol daily x 14days

Placebo DRUG

Safflower oil capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-50 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 20% fall in Forced Expiratory Volume in 1 second (FEV1) (PC20 methacholine) by the method used in a separate screening protocol.
• FEV1 of at least 80% of predicted and FEV1/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.
• Symptom Score (this will be submitted as an attachment) no greater than 16 (out of a possible 24) 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.

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 12 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 National Heart, Lung and Blood Institute (NHLBI) guidelines for diagnosis and management of asthma. (Not to include prophylactic use of albuterol prior to exercise).
• Viral upper respiratory tract infection within 2 weeks of challenge.
• Any acute infection requiring antibiotics within 2 weeks of exposure or fever of unknown origin within 2 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 Clinical Center Reference Endotoxin (CCRE) exposure, interfere with any other medications potentially used in the study (to include 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, including E coli, 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
• Purdue University: collaborator

Study Sites (1)

Center for Environmental Medicine, Asthma and Lung Biology

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• Burbank AJ, Duran CG, Pan Y, Burns P, Jones S, Jiang Q, Yang C, Jenkins S, Wells H, Alexis N, Kesimer M, Bennett WD, Zhou H, Peden DB, Hernandez ML. Gamma tocopherol-enriched supplement reduces sputum eosinophilia and endotoxin-induced sputum neutrophilia in volunteers with asthma. J Allergy Clin Immunol. 2018 Apr;141(4):1231-1238.e1. doi: 10.1016/j.jaci.2017.06.029. Epub 2017 Jul 20.

  PMID: 28736267 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

gamma-Tocopherol

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tocopherols; Vitamin E; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Allison Burbank, MD
• Organization: Center for Environmental Medicine, Asthma and Lung Biology; University of North Carolina, Chapel Hill

allison_burbank@med.unc.edu

919-843-2714

Study Officials

• David B Peden, MD, MS

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2014
• First Posted: April 4, 2014
• Study Start: November 1, 2015
• Primary Completion: September 1, 2016
• Study Completion: August 1, 2017
• Last Updated: November 6, 2017
• Results First Posted: November 6, 2017

Record last verified: 2017-09

Locations

US (1)