A Double-Blind Randomized Placebo Controlled Trial Investigating the Effects of DSM17938 on Capsaicin Evoked Coughs
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Atopic Asthma
- Sponsor
- McMaster University
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Emax
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
Cough in asthma is a very common and troublesome symptom in asthma, which predicts severity and poor prognosis. Previous studies have shown that asthmatics have an exaggerated cough response to capsaicin. Currently available asthma treatment is not designed to target the cough reflex directly, so this presents an unmet need for patients. The treatment being tested in this study is the commercially available over the counter oral probiotic BioGaia® DSM17938. Based on clinical and pre-clinical evidence, it is hypothesized that TRPV1 antagonism with BioGaia® DSM17938 will result in a reduction in capsaicin evoked coughs in patients with asthma.
Detailed Description
Visit 1: Baseline Screening and Beginning of Treatment Period 1 Subjects will undergo consent, complete history, physical examination, spirometry, capsaicin cough challenge, skin prick testing (allergen and histamine), methacholine challenge, induced sputum and blood sampling. Eligible subjects will then be randomized with matched oral BioGaia DSM17938 and placebo and will be given for the next 4 weeks. Visit 2: End of Treatment Period 1 Subjects will undergo spirometry, capsaicin cough challenge, skin prick testing, methacholine challenge, sputum induction and blood testing. Washout: 28 day washout period prior to Visit 3. Visit 3: Beginning of Treatment Period 2 Subjects wills undergo all the same tests performed in visit 2. Drug/Placebo will be given for the next 28 days. Visit 4: End of Treatment Period 2 Subjects will undergo all the same tests performed in visit 2.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Able to understand and give written informed consent
- •Has a diagnosis of atopic asthma (based on at least one positive skin prick test and Methacholine PC20 ≤16 mg/ml)
- •FEV1 (forced expiratory volume at 1 second) ≥ 70% of predicted
- •Demonstrate a cough response to capsaicin
Exclusion Criteria
- •Subjects who are in a pollen season that affects their asthma
- •Subjects who bronchoconstrict by more than 10% at the end of the full dose capsaicin cough challenge (assess after visit 1)
- •Subjects who do not display evidence of airway hyper-responsiveness (PC20\>16mg/ml) (assess after visit 1)
- •Symptoms of upper respiratory tract infection (URTI) in the last 1 month which have not resolved.
- •Lower respiratory tract infection or pneumonia in the last 6 weeks.
- •Current smoker or ex-smoker with ≥10 pack year smoking history and abstinence of ≤6 months
- •Asthma exacerbation in the previous month requiring an increase or start of an ICS (inhaled corticosteroids) or OCS (oral corticosteroids)
- •Any asthma medication with the exception of infrequent (less than twice weekly) short-acting beta-agonist.
- •Subjects who have changed asthma medication within the past 4 weeks prior to screening
- •A previous asthma exacerbation requiring Intensive Care Unit (ICU) admission.
Outcomes
Primary Outcomes
Emax
Time Frame: Day 1, Day 30, Day 59 and Day 89
The maximum number of capsaicin evoked coughs
Secondary Outcomes
- ED50 (median effective dose)(Day 1, Day 30, Day 59 and Day 89)
- C2 and C5(Day 1, Day 30, Day 59 and Day 89)
- T-Cell Cytokine(Day 1, Day 30, Day 59 and Day 89)
- Itch Intensity(Day 1, Day 30, Day 59 and Day 89)
- Dose response(Day 1, Day 30, Day 59 and Day 89)
- Responses to histamine(Day 1, Day 30, Day 59 and Day 89)
- Sputum differential cell counts(Day 1, Day 30, Day 59 and Day 89)
- PC20(Day 1, Day 30. Day 59 and Day 89)