Probiotics and Capsaicin Evoked Coughs

Not Applicable

Completed

• Conditions: Atopic Asthma
• Interventions: Dietary Supplement: BioGaia-DSM17938

• Registration Number: NCT03603522
• Lead Sponsor: McMaster University

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-07-18
• Study First Submitted QC: 2018-07-18
• Study First Posted: 2018-07-27
• Status Verified: 2019-03
• Study Start: 2019-07-16
• Primary Completion: 2021-01-18
• Study Completion: 2021-01-18
• Last Update Submitted: 2021-03-25
• Last Update Posted: 2021-03-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo Comparator then BioGaia DSM17938	BioGaia-DSM17938	28 days treatment with placebo comparator treatment, followed by 28 days washout and then crossover to 28 days treatment with BioGaia DSM17938.
BioGaia-DSM17938 then Placebo Comparator	BioGaia-DSM17938	28 days treatment with BioGaia-DSM17938, followed by 28 days washout and then crossover to 28 days placebo comparator treatment.

Primary Outcome Measures

Name	Time	Method
Emax	Day 1, Day 30, Day 59 and Day 89	The maximum number of capsaicin evoked coughs

Secondary Outcome Measures

Name	Time	Method
ED50 (median effective dose)	Day 1, Day 30, Day 59 and Day 89	The dose of capsaicin that evokes at least half the maximum number of coughs
C2 and C5	Day 1, Day 30, Day 59 and Day 89	Changes in the dose of capsaicin causing 2 coughs (C2) and 5 coughs (C5)
T-Cell Cytokine	Day 1, Day 30, Day 59 and Day 89	Inhibition of T-Cell cytokine responses to stimulation in blood
Itch Intensity	Day 1, Day 30, Day 59 and Day 89	The intensity of itch after skin prick testing using a modified Borg scale (0-10)
Dose response	Day 1, Day 30, Day 59 and Day 89	Changes in the capsaicin full dose response curves
Responses to histamine	Day 1, Day 30, Day 59 and Day 89	The wheal responses to graded doses of histamine skin prick testing
Sputum differential cell counts	Day 1, Day 30, Day 59 and Day 89	Changes in sputum differential cell counts
PC20	Day 1, Day 30. Day 59 and Day 89	Changes in methacholine PC20

Trial Locations

Locations (1)

McMaster Cardio-Respiratory Research Lab; 🇨🇦 Hamilton, Ontario, Canada