Effect of Sex Hormone During the Menstrual Cycle on Capsaicin Evoked Cough Responses

NCT ID: NCT04233762

Last Updated: 2024-03-01

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 32 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-01-08
• Study Completion Date: 2022-05-30

Brief Summary

The study aim is to investigate if changes in sex hormones during the menstrual cycle affects cough sensitivity in females and males with mild allergic asthma. Female subjects will be grouped according to natural cycle, or taking oral contraceptives. Male subjects will act as the control group.

Detailed Description

The study will have a total of 3 visits separated by at least 24 hours. Screening Period (Visits 1) - For All Subjects. Eligible subjects will be identified during the initial screening procedures with measures of spirometry, hyperresponsiveness to methacholine, complete history, physical examination, allergen skin test, and capsaicin cough challenge. For female subjects, this visit will occur during Day 1-5 (follicular phase) of the menstrual cycle. Subjects meeting the eligibility criteria will be randomized to Sequence A or Sequence B.

Sequence A will require Visit 2 to occur during menstrual cycle days 1-5 (follicular phase) and Visit 3 to occur during menstrual cycle days 21 - 25 (luteal phase).

Sequence B will require Visit 2 to occur during menstrual cycle days 21-25 (luteal phase) and Visit 3 to occur during menstrual cycle days 1 - 5 (follicular phase).

During Visit 2 and 3 subjects will undergo measures of spirometry, hyperresponsiveness to methacholine, capsaicin cough challenge, allergen skin test, sputum and blood collection.

Visit Windows Each visit must be separated by a minimum of 24 hours. Study visits can be performed in the morning or afternoon, however for each subject the timing should be consistent with Visit 1 at the same time of day ± 2 hours.

Conditions

Asthma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Female Natural Cycle Group

Females with regular natural menstrual cycle.

No interventions assigned to this group

Female Oral Contraceptive Pill Group

Females taking the combined oral contraceptive pill.

No interventions assigned to this group

Male Group

Males with no history of anabolic steroid use.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

1. Subjects must be aged between 18 to 35 years

2. Have a diagnosis of atopic asthma (based on at least one positive skin prick test and methacholine PC20 ≤16 mg/ml)

3. FEV1 ≥ 70% of predicted

4. Demonstrate a cough response to capsaicin with a minimum of 3 coughs during the screening capsaicin challenge

Exclusion Criteria

1. Subjects who are in a pollen season that affects their asthma

2. Subjects who report allergies to capsaicin or bronchoconstrict at the end of the full dose capsaicin cough challenge and require short acting bronchodilator therapy (assess after visit 1)

3. Subjects who do not display evidence of airway hyper-responsiveness (methacholine PC20>16mg/ml) (assess after visit 1)

4. Symptoms of upper respiratory tract infection in the last 1 month which have not resolved.

5. Lower respiratory tract infection or pneumonia in the last 6 weeks.

6. Current smoker or ex-smoker with ≥10 pack year smoking history and abstinence of ≤6 months

7. Asthma exacerbation in the previous month requiring a start of inhaled or oral corticosteroids.

8. Any asthma medication with the exception of infrequent (less than twice weekly) short-acting β2-agonist.

9. Subjects who have changed asthma medication within the past 4 weeks prior to screening

10. A previous asthma exacerbation requiring Intensive Care Unit admission.

11. Significant other primary pulmonary disorders in particularly; pulmonary embolism, pulmonary hypertension, interstitial lung disease, lung cancer, cystic fibrosis, emphysema or bronchiectasis.

12. Pregnancy or breast-feeding

13. Use of ACE inhibitors

14. Any centrally acting medication (opioids, gapapentin, pregabalin, amitriptyline) which in the view of the investigator could alter the sensitivity of the cough reflex

15. History of psychiatric illness, drug or alcohol abuse which may interfere in the participation of the trial.

16. History of current or previous anabolic steroid use in men.

17. For the natural cycle group, the female patients must have regular (24 to 35 day) natural cycles and no oral contraceptive use for ≥6 months

18. For female's taking the oral contraceptive pill they must be taking this ≥6 months

19. Use of B-blockers

20. Patients with clinically significant cardiovascular disease

21. Patients with known allergy to any of the study medications or excipients

22. Patients with a known potentially life threatening allergy (e.g. food allergy, stinging insect allergy), history of anaphylaxis, mastocytosis, angioedema

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gail Gauvreau, PhD

Role: PRINCIPAL_INVESTIGATOR

Professor Department of Medicine

Locations

McMaster Cardio-Respiratory Research Lab

Hamilton, Ontario, Canada

Countries

Canada

Other Identifiers

McMaster-CASH

Identifier Type: -

Identifier Source: org_study_id