Clinical trial: Effect of Gamma Tocopherol Enriched Supplementation on Response to Inhaled O3 Exposure (NCT02911688)

Eligibility criteria:
Inclusion Criteria:

          1. Age 18-45 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 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.

          5. 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.

          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; or a clinical history consistent with seasonal or
             perennial allergy symptoms.

          7. 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.

          8. 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.

          9. 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.

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        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
             3 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 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 4 weeks of challenge.

          7. Any acute infection requiring antibiotics within 4 weeks of exposure or fever of
             unknown origin within 4 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 O3 exposure, interfere with any other
             medications potentially used in the study (to include systemic 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, 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 (IUD, birth control
             pills/patch, condoms).

         17. Abnormal Prothrombin Time (PT) or activated Partial Thromboplastin Time (aPTT) 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. Orthopedic conditions which would prevent the volunteer from performing moderate
             exercise on a treadmill.

         20. 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.

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No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 45 Years

Patient description (medical language): A 30-year-old man who is a computer scientist came to the clinic with the lab result stating azoospermia.  The patient is sexually active with his wife and does not use any contraception methods.  They have been trying to conceive for the past year with no success.  The patient has a past medical history of recurrent pneumonia, shortness of breath, and  persistent cough that produces large amounts of thick sputum. The patient had multiple lung infections during childhood. He does not smoke, use illicit drugs or alcohol.  The patient has no history of other medical conditions including allergies or any kind of surgery.  On physical examination, the digits show clubbing.  An ultrasound shows bilateral absence of the vas deferens, and FEV1 was 75% on the respiratory function test.

Patient description (patient's own words): I'm a 30-year-old computer scientist. I did some lab tests that came back quite alarming, stating that I have azoospermia?! I'm sexually active with my wife and we don't use contraception. We've been trying to have a child for the past year. I have a medical history of pneumonia and shortness of breath and regular wet cough. I had several lung infections when I was a kid. That's why I'm very careful and don't smoke, do drugs, or drink. I don't have other medical conditions including allergies or any kind of surgery. The doctor did the clubbing test on my fingers, which was positive. I also did an ultrasound and it showed that I'm missing the tubes that carry sperm around. I also had a 75% for my respiratory function test.

Does the patient match the trial criteria? Contradiction