The Effects of Salbutamol on Mannitol Induced Cough Responses in Healthy Controls

NCT ID: NCT04565847

Last Updated: 2022-06-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-30
• Study Completion Date: 2021-12-16

Brief Summary

The study aim is to investigate if changes in osmolarity using mannitol challenge can evoke coughing healthy controls with no evidence of bronchoconstriction (PC20>16mg/ml or mannitol PD15 > 635 mg, or < 10% incremental fall in FEV1 between consecutive mannitol doses) and if salbutamol can affect this. This is a double-blind, placebo-controlled analysis in healthy controls assessing the effects of salbutamol on mannitol induced cough.

Detailed Description

The study will have a maximum of 4 visits separated by at least 24 hours. The first 2 visits will determine eligibility. All eligible subjects will be invited back for a third and a fourth visit.

Screening Period (Visits 1 and 2) - 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 mannitol cough challenge. The screening procedures will be conducted over 2 separate visits.

Effects of Salbutamol (Visit 3 and 4) - For Healthy Control Subjects, Twenty subjects with no evidence of asthma will return for visit 3 and 4. These visits must be at least 24h apart and no longer than 7 days. Health controls will first receive salbutamol 2.5mg or saline placebo via a nebuliser and 15 mins later the forced expiratory volume at one second (FEV1) measured. Subjects will then undergo a mannitol cough challenge exactly like the previous mannitol cough challenges. These data will be used for determining the effects of salbutamol on mannitol-induced cough.

Visit Windows Each visit must be separated by a minimum of 24 hours, and a maximum of 7 days. Study visits can be performed in the morning or afternoon, however for each subject the timing should be consistent with Visits 2 at the same time of day ± 2 hours

Conditions

Cough

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Healthy Control - Active Arm

Healthy Controls Mannitol-Induced Cough Challenges on Visit 2 to determine elligibility (cough response). Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. Nebulized salbutamol (5mg/mL) given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4.

Group Type: ACTIVE_COMPARATOR

Salbutamol 5mg/mL

Intervention Type: DRUG

Nebulized salbutamol given prior to Mannitol-Induced Cough Challenge

Healthy control - Placebo Arm

Healthy Controls Mannitol-Induced Cough Challenges on Visit 2 to determine elligibility (cough response). Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. Nebulized 0.9% Saline given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4.

Group Type: PLACEBO_COMPARATOR

Sodium Chloride 0.9% Inhl 3Ml

Intervention Type: DRUG

Nebulized 0.9% saline given prior to Mannitol-Induced Cough Challenge

Interventions

Salbutamol 5mg/mL

Nebulized salbutamol given prior to Mannitol-Induced Cough Challenge

Intervention Type: DRUG

Sodium Chloride 0.9% Inhl 3Ml

Nebulized 0.9% saline given prior to Mannitol-Induced Cough Challenge

Intervention Type: DRUG

Other Intervention Names

Ventolin nebuliser; Placebo Comparator

Eligibility Criteria

Inclusion Criteria

1. Able to understand and give written informed consent.

2. Male and female volunteers 18 through 65 years of age.

3. No airway hyperresponsiveness as determined by methacholine PC20>16mg/ml or mannitol PD15 > 635 mg, or < 10% incremental fall in FEV1 between consecutive mannitol doses.

4. Fall in FEV1 of ≤ 5% after any mannitol dose during mannitol challenge compared to baseline FEV1 at 0 mg at screening mannitol challenge (Visit 2).

5. Baseline FEV1≥ 80% of the predicted value.

6. Demonstrate cough response to inhaled mannitol.

Exclusion Criteria

1. Current or former smoker with >10-pack-year history

2. Current or previous history of other significant respiratory disease

3. Significant systemic disease, including history of current malignancy or autoimmune disease

4. Pregnancy or breastfeeding.

5. Use of corticosteroids within 28 days prior to the first study visit.

6. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 48 hours of study visits or aspirin with 7 days of study visits

7. Use of antihistamines including those in cold and allergy medications within 72 hours of study visits

8. Use of caffeine-containing products within 4 hours of study visits

9. Use of ACE inhibitors

10. Any centrally acting medication which in the view of the investigator could alter the sensitivity of the cough reflex including but not restricted to tricyclic anti-depressants, pregabalin, gabapentin, codeine, tramadol, or any other opioid.

11. Unwillingness or inability to comply with the study protocol for any other reason

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Gail Gauvreau

Professor Department of MEdicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gail Gauvreau, PhD

Role: PRINCIPAL_INVESTIGATOR

McMaster University Hospital

Locations

McMaster Cardio-Respiratory Research Lab

Hamilton, Ontario, Canada

McMaster University

Hamilton, Ontario, Canada

Countries

Canada

Other Identifiers

McMaster-COMA-11537

Identifier Type: -

Identifier Source: org_study_id