A Study of Gamma Tocopherol-enriched Supplement on Lower Airway Responses to Inhaled Wood Smoke in Healthy Adults

NCT03444298 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 17-23035R01ES025124
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose: To determine the efficacy of 1400 mg gamma tocopherol-enriched supplement for mitigating inhaled wood smoke particle-induced airway inflammation in healthy adults with no more than mild asthma.

Conditions

Airway Inflammation; Asthma

Outcome Measures

Primary Outcomes (2)

• Change in Sputum % Polymorphonuclear Neutrophils (PMN) With Wood Smoke Particulate (WSP) Exposure

  A comparison of the WSP-induced change in sputum % PMNs (Post-WSP sputum - Pre-WSP sputum) during gamma tocopherol treatment with the WSP-induced change in sputum % PMNs during placebo treatment.

  baseline, and 4 hours post exposure

• Change in Sputum % PMNs With WSP Exposure

  A comparison of the WSP-induced change in sputum % PMNs (Post-WSP sputum - Pre-WSP sputum) during gamma tocopherol treatment with the WSP-induced change in sputum % PMNs during placebo treatment.

  baseline, and 24 hours post exposure

Secondary Outcomes (2)

• Change in Absolute PMN Count (ANC) in Sputum With WSP Exposure

  baseline, and 4 hours post exposure

• Change in Absolute PMN Count (ANC) in Sputum With WSP Exposure

  baseline, and 24 hours post exposure

Study Arms (2)

Placebo first, then Gamma Tocopherol

PLACEBO COMPARATOR

Participants that are randomized to placebo treatment will take a short treatment course of Neutral Oil followed by chamber exposure with wood smoke particulate. After a 4-week washout period, participants will cross over to the gamma Tocopherol (active) treatment group.

Drug: Gamma Tocopherol; Drug: Placebo

GammaTocopherol first, then Placebo

ACTIVE COMPARATOR

Participants that are randomized γT treatment will take a short treatment course of gamma Tocopherol followed by chamber exposure with WSP. After a 4-week washout period, participants will cross over to the placebo treatment group.

Drug: Gamma Tocopherol; Drug: Placebo

Interventions

Gamma Tocopherol DRUG

Each dose consists of two (700 mg) capsules by mouth once daily for a total of 7 days.

Also known as: Vitamin E

GammaTocopherol first, then Placebo; Placebo first, then Gamma Tocopherol

Placebo DRUG

Each dose consists of two capsules by mouth once daily for a total of 7 days.

Also known as: Neutral oil

GammaTocopherol first, then Placebo; Placebo first, then Gamma Tocopherol

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-45 years, inclusive, of both genders
• Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy
• Forced expiratory volume at one second (FEV1) of at least 75% of predicted (without use of bronchodilating medications for 12 hours), consistent with lung function of persons with no more than mild intermittent or mild persistent asthma.
• Oxygen saturation of \<93% and blood pressure within the following limits: (Systolic between 150-85 mmHg, Diastolic between 90-50 mmHg).
• Ability to provide an induced sputum sample.
• Subject must demonstrate a ≥10% increase in sputum neutrophils following inhaled WSP exposure, when compared to baseline sputum (to be completed in a separate protocol).
• Ability/willingness to discontinue inhaled corticosteroids, montelukast, and cromolyn for 2 weeks without increased symptoms or increased need for beta agonist rescue medication prior to screening and through the course of the study.

You may not qualify if:

• Patients who meet any of these criteria are not eligible for enrollment as study participants:
• Clinical contraindications:
• 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.
• 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.
• Abnormal physical findings at the baseline visit, including but not limited to abnormalities on auscultation, temperature of 37.8° C, Systolic BP \> 150mm Hg or \< 85 mm Hg; or Diastolic BP \> 90 mm Hg or \< 50 mm Hg, or pulse oximetry saturation reading less than 93%.
• Physician directed emergency treatment for an asthma exacerbation within the preceding 12 months.
• Moderate or severe asthma
• Exacerbation of asthma more than 2x/weeks which would be characteristic of a person with moderate or severe persistent asthma as outlined in the current National Asthma Education and Prevention Program (NAEPP) 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 with 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).
• 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 the diagnosis and management of asthma.
• History of intubation for asthma
• If there is a history of allergic rhinitis, subjects must be asymptomatic of allergic rhinitis at the time of study enrollment.
• 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.
• Cigarette smoking \> 1 pack per month

Sponsors & Collaborators

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

Study Sites (1)

UNC Center for Environmental Medicine, Asthma and Lung Biology

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (5)

• Burbank AJ, Duran CG, Almond M, Wells H, Jenkins S, Jiang Q, Yang C, Wang T, Zhou H, Hernandez ML, Peden DB. A short course of gamma-tocopherol mitigates LPS-induced inflammatory responses in humans ex vivo. J Allergy Clin Immunol. 2017 Oct;140(4):1179-1181.e4. doi: 10.1016/j.jaci.2017.04.030. Epub 2017 May 12. No abstract available.

  PMID: 28506847 BACKGROUND

• Hernandez ML, Wagner JG, Kala A, Mills K, Wells HB, Alexis NE, Lay JC, Jiang Q, Zhang H, Zhou H, Peden DB. Vitamin E, gamma-tocopherol, reduces airway neutrophil recruitment after inhaled endotoxin challenge in rats and in healthy volunteers. Free Radic Biol Med. 2013 Jul;60:56-62. doi: 10.1016/j.freeradbiomed.2013.02.001. Epub 2013 Feb 9.

  PMID: 23402870 BACKGROUND

• Wiser J, Alexis NE, Jiang Q, Wu W, Robinette C, Roubey R, Peden DB. In vivo gamma-tocopherol supplementation decreases systemic oxidative stress and cytokine responses of human monocytes in normal and asthmatic subjects. Free Radic Biol Med. 2008 Jul 1;45(1):40-9. doi: 10.1016/j.freeradbiomed.2008.03.002. Epub 2008 Mar 12.

  PMID: 18405673 BACKGROUND

• 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 BACKGROUND

• Peden DB, Almond M, Brooks C, Robinette C, Wells H, Burbank A, Hernandez M, Hinderliter A, Caughey M, Jiang Q, Wang Q, Li H, Zhou H, Alexis N. A pilot randomized clinical trial of gamma-tocopherol supplementation on wood smoke-induced neutrophilic and eosinophilic airway inflammation. J Allergy Clin Immunol Glob. 2023 Oct 5;2(4):100177. doi: 10.1016/j.jacig.2023.100177. eCollection 2023 Nov.

  PMID: 37876758 RESULT

MeSH Terms

Conditions

Asthma

Interventions

gamma-Tocopherol; Vitamin E

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Carole Robinette
• Organization: University of North Carolina at Chapel Hill

carole_robinette@med.unc.edu

919-966-5638

Study Officials

• David Peden, MD

  UNC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The randomization schedule will be generated by the biostatistician and provided to the investigational pharmacy. Only the biostatistician and the pharmacist will have access to the randomization schedule. Participants will consume 1400 mg of γT-enriched supplement or matching placebo once daily for 7 days.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects will be allocated to begin the first period of the crossover study with placebo or gamma tocopherol treatment using permuted block randomization with a block size of 4 (2 placebo, 2 gamma tocopherol for the first treatment period of the protocol).

Study Record Dates

• First Submitted: January 31, 2018
• First Posted: February 23, 2018
• Study Start: June 8, 2018
• Primary Completion: March 2, 2023
• Study Completion: March 6, 2023
• Last Updated: February 5, 2024
• Results First Posted: February 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)