Clinical trial NCT03603522: Probiotics and Capsaicin Evoked Coughs
Official title: A Double-Blind Randomized Placebo Controlled Trial Investigating the Effects of DSM17938 on Capsaicin Evoked Coughs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Atopic Asthma
Keywords: Cough
Capsaicin
Probiotics
TRPV1
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: BioGaia AB
First posted: 2018-07-27
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants will have a screening period followed by 28 days treatment with BioGaia DSM17938 or placebo, followed by a washout period and will then crossover to the opposite treatment received in the first part of the study.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Aged ≥18
2. Able to understand and give written informed consent
3. Has a diagnosis of atopic asthma (based on at least one positive skin prick test and Methacholine PC20 ≤16 mg/ml)
4. FEV1 (forced expiratory volume at 1 second) ≥ 70% of predicted
5. Demonstrate a cough response to capsaicin

Exclusion Criteria:

1. Subjects who are in a pollen season that affects their asthma
2. Subjects who bronchoconstrict by more than 10% at the end of the full dose capsaicin cough challenge (assess after visit 1)
3. Subjects who do not display evidence of airway hyper-responsiveness (PC20\>16mg/ml) (assess after visit 1)
4. Symptoms of upper respiratory tract infection (URTI) 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 an increase or start of an ICS (inhaled corticosteroids) or OCS (oral corticosteroids)
8. Any asthma medication with the exception of infrequent (less than twice weekly) short-acting beta-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 (ICU) 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 (angiotensin converting enzyme) inhibitors
14. Any centrally acting medication 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.

Primary outcomes:
measure: Emax
timeFrame: Day 1, Day 30, Day 59 and Day 89
Secondary outcomes:
measure: ED50 (median effective dose)
timeFrame: Day 1, Day 30, Day 59 and Day 89
measure: Dose response
timeFrame: Day 1, Day 30, Day 59 and Day 89
measure: C2 and C5
timeFrame: Day 1, Day 30, Day 59 and Day 89
measure: Responses to histamine
timeFrame: Day 1, Day 30, Day 59 and Day 89
measure: Itch Intensity
timeFrame: Day 1, Day 30, Day 59 and Day 89
measure: T-Cell Cytokine
timeFrame: Day 1, Day 30, Day 59 and Day 89
measure: Sputum differential cell counts
timeFrame: Day 1, Day 30, Day 59 and Day 89
measure: PC20
timeFrame: Day 1, Day 30. Day 59 and Day 89
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster Cardio-Respiratory Research Lab
state: Ontario
Study officials:
affiliation: McMaster University
name: Gail Gauvreau, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Satia I, Cusack R, Stevens C, Schlatman A, Wattie J, Mian F, Killian KJ, O'Byrne PM, Bienenstock J, Forsythe P, Gauvreau GM. Limosilactobacillus reuteri DSM-17938 for preventing cough in adults with mild allergic asthma: A double-blind randomized placebo-controlled cross-over study. Clin Exp Allergy. 2021 Sep;51(9):1133-1143. doi: 10.1111/cea.13976. Epub 2021 Jul 8.