Overview

Effect of Gamma Tocopherol Enriched Supplementation on Response to Inhaled LPS

Status:
Completed
Trial end date:
2017-08-01
Target enrollment:
0
Participant gender:
All
Summary
To test the hypothesis that gamma tocopherol (vitamin E) supplement inhibits endotoxin induced airways inflammation in allergic asthmatics
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of North Carolina, Chapel Hill
Collaborators:
National Institute of Environmental Health Sciences (NIEHS)
Purdue University
Treatments:
alpha-Tocopherol
gamma-Tocopherol
Tocopherols
Tocotrienols
Vitamin E
Criteria
Inclusion Criteria:

1. Age 18-50 of both genders

2. Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy

3. History of episodic wheezing, chest tightness, or shortness of breath consistent with
asthma, or physician diagnosed asthma.

4. 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.

5. 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.

6. 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.

7. 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.

8. subjects must be willing to avoid caffeine for 12 hours prior to all visits.

Exclusion Criteria:

1. 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

2. Physician directed emergency treatment for an asthma exacerbation within the preceding
12 months

3. Moderate or Severe asthma

4. 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.

5. 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).

6. Viral upper respiratory tract infection within 2 weeks of challenge.

7. Any acute infection requiring antibiotics within 2 weeks of exposure or fever of
unknown origin within 2 weeks of challenge.

8. Severe asthma

9. 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.

10. 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)

11. Any history of smoking in the year prior to study enrollment; lifetime smoking history
> 10 pack years

12. 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

13. Allergy/sensitivity to study drugs, including E coli, or their formulations.

14. Known hypersensitivity to methacholine or to other parasympathomimetic agents

15. History of intubation for asthma

16. Unwillingness to use reliable contraception if sexually active (Intrauterine device,
birth control pills/patch, condoms).

17. Abnormal Prothrombin Time (PT) or Partial Thromboplastin Time (PTT) values at
screening or during the treatment period. Normal values will be those published by the
clinical lab (Labcorp, INC).

18. Any bleeding disorder

19. Radiation exposure history will be collected. Subjects whose exposure history within
the past twelve months would cause them to exceed their annual limits will be
excluded.

20. Pregnancy