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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma

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.

• Study Type: Observational
• Enrollment (Actual): 32

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster Cardio-Respiratory Research Lab

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 31 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Mild atopic asthmatics

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Female Natural Cycle Group; Females with regular natural menstrual cycle.
Female Oral Contraceptive Pill Group; Females taking the combined oral contraceptive pill.
Male Group; Males with no history of anabolic steroid use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Emax	The maximum number of capsaicin evoked coughs	One visit during day 1 to day 5 of the menstrual cycle, compared to one visit during day 21 to 25 of the menstrual cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ED 50	The dose of capsaicin that evokes at least half the maximum number of coughs(ED50) in days 1 -5 and 21 - 25 of the natural cycle, and between the natural cycle, male subjects and female subjects taking the oral contraceptive pill	One visit during day 1 to day 5 of the menstrual cycle, compared to one visit during day 21 to 25 of the menstrual cycle
Dose response Curve	Changes in the capsaicin full dose response curves	One visit during day 1 to day 5 of the menstrual cycle, compared to one visit during day 21 to 25 of the menstrual cycle
C2 and C5	Changes in the dose of capsaicin causing 2 coughs (C2) and 5 coughs (C5)	One visit during day 1 to day 5 of the menstrual cycle, compared to one visit during day 21 to 25 of the menstrual cycle

Collaborators and Investigators

• Sponsor: McMaster University
• Investigators: Principal Investigator: Gail Gauvreau, PhD, Professor Department of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2020
• Primary Completion (Actual): May 30, 2022
• Study Completion (Actual): May 30, 2022

Study Registration Dates

• First Submitted: January 8, 2020
• First Submitted That Met QC Criteria: January 16, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: McMaster-CASH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No