Probiotics and Capsaicin Evoked Coughs (PCEC)

A Double-Blind Randomized Placebo Controlled Trial Investigating the Effects of DSM17938 on Capsaicin Evoked Coughs

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.

Study Overview

• Status: Completed
• Conditions: Atopic Asthma
• Intervention / Treatment: Dietary supplement: BioGaia-DSM17938; Other: Placebo Comparator: Placebo Control

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

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: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BioGaia-DSM17938 then Placebo Comparator; 28 days treatment with BioGaia-DSM17938, followed by 28 days washout and then crossover to 28 days placebo comparator treatment.	Dietary supplement: BioGaia-DSM17938; 2mL per day (1x10^9 CFU) per day taken orally for 28 days; Other: Placebo Comparator: Placebo Control; 2mL per day of placebo formulation taken orally for 28 days
PLACEBO_COMPARATOR: Placebo Comparator then BioGaia DSM17938; 28 days treatment with placebo comparator treatment, followed by 28 days washout and then crossover to 28 days treatment with BioGaia DSM17938.	Dietary supplement: BioGaia-DSM17938; 2mL per day (1x10^9 CFU) per day taken orally for 28 days; Other: Placebo Comparator: Placebo Control; 2mL per day of placebo formulation taken orally for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Emax	The maximum number of capsaicin evoked coughs	Day 1, Day 30, Day 59 and Day 89

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: BioGaia AB

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 16, 2019
• Primary Completion (ACTUAL): January 18, 2021
• Study Completion (ACTUAL): January 18, 2021

Study Registration Dates

• First Submitted: July 18, 2018
• First Submitted That Met QC Criteria: July 18, 2018
• First Posted (ACTUAL): July 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 26, 2021
• Last Update Submitted That Met QC Criteria: March 25, 2021
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Probiotics; Cough; Capsaicin; TRPV1
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough
• Other Study ID Numbers: McMaster- DSM17938-5095

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
• product manufactured in and exported from the U.S.: No