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Probiotics and Capsaicin Evoked Coughs (PCEC)

Primary Purpose

Atopic Asthma

Status

Completed

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

BioGaia-DSM17938

Placebo Comparator: Placebo Control

About this trial

This is an interventional treatment trial for Atopic Asthma focused on measuring Cough, Capsaicin, Probiotics, TRPV1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Aged ≥18
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.
Significant other primary pulmonary disorders in particularly; pulmonary embolism, pulmonary hypertension, interstitial lung disease, lung cancer, cystic fibrosis, emphysema or bronchiectasis.
Pregnancy or breast-feeding
Use of ACE (angiotensin converting enzyme) inhibitors
Any centrally acting medication which in the view of the investigator could alter the sensitivity of the cough reflex
History of psychiatric illness, drug or alcohol abuse which may interfere in the participation of the trial.

Sites / Locations

McMaster Cardio-Respiratory Research Lab

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

BioGaia-DSM17938 then Placebo Comparator

Placebo Comparator then BioGaia DSM17938

Arm Description

28 days treatment with BioGaia-DSM17938, followed by 28 days washout and then crossover to 28 days placebo comparator treatment.

28 days treatment with placebo comparator treatment, followed by 28 days washout and then crossover to 28 days treatment with BioGaia DSM17938.

Outcomes

Primary Outcome Measures

Emax

The maximum number of capsaicin evoked coughs

Secondary Outcome Measures

ED50 (median effective dose)

The dose of capsaicin that evokes at least half the maximum number of coughs

Dose response

Changes in the capsaicin full dose response curves

C2 and C5

Changes in the dose of capsaicin causing 2 coughs (C2) and 5 coughs (C5)

Responses to histamine

The wheal responses to graded doses of histamine skin prick testing

Itch Intensity

The intensity of itch after skin prick testing using a modified Borg scale (0-10)

T-Cell Cytokine

Inhibition of T-Cell cytokine responses to stimulation in blood

Sputum differential cell counts

Changes in sputum differential cell counts

PC20

Changes in methacholine PC20

Full Information

NCT ID

NCT03603522

First Posted

July 18, 2018

Last Updated

March 25, 2021

Sponsor

McMaster University

Collaborators

BioGaia AB

1. Study Identification

Unique Protocol Identification Number

NCT03603522

Brief Title

Probiotics and Capsaicin Evoked Coughs

Acronym

PCEC

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

July 16, 2019 (Actual)

Primary Completion Date

January 18, 2021 (Actual)

Study Completion Date

January 18, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

McMaster University

Collaborators

BioGaia AB

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Atopic Asthma

Keywords

Cough, Capsaicin, Probiotics, TRPV1

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

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.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BioGaia-DSM17938 then Placebo Comparator

Arm Type

Experimental

Arm Description

28 days treatment with BioGaia-DSM17938, followed by 28 days washout and then crossover to 28 days placebo comparator treatment.

Arm Title

Placebo Comparator then BioGaia DSM17938

Arm Type

Placebo Comparator

Arm Description

28 days treatment with placebo comparator treatment, followed by 28 days washout and then crossover to 28 days treatment with BioGaia DSM17938.

Intervention Type

Dietary Supplement

Intervention Name(s)

BioGaia-DSM17938

Intervention Description

2mL per day (1x10^9 CFU) per day taken orally for 28 days

Intervention Type

Other

Intervention Name(s)

Placebo Comparator: Placebo Control

Intervention Description

2mL per day of placebo formulation taken orally for 28 days

Primary Outcome Measure Information:

Title

Emax

Description

The maximum number of capsaicin evoked coughs

Time Frame

Day 1, Day 30, Day 59 and Day 89

Secondary Outcome Measure Information:

Title

ED50 (median effective dose)

Description

The dose of capsaicin that evokes at least half the maximum number of coughs

Time Frame

Day 1, Day 30, Day 59 and Day 89

Title

Dose response

Description

Changes in the capsaicin full dose response curves

Time Frame

Day 1, Day 30, Day 59 and Day 89

Title

C2 and C5

Description

Changes in the dose of capsaicin causing 2 coughs (C2) and 5 coughs (C5)

Time Frame

Day 1, Day 30, Day 59 and Day 89

Title

Responses to histamine

Description

The wheal responses to graded doses of histamine skin prick testing

Time Frame

Day 1, Day 30, Day 59 and Day 89

Title

Itch Intensity

Description

The intensity of itch after skin prick testing using a modified Borg scale (0-10)

Time Frame

Day 1, Day 30, Day 59 and Day 89

Title

T-Cell Cytokine

Description

Inhibition of T-Cell cytokine responses to stimulation in blood

Time Frame

Day 1, Day 30, Day 59 and Day 89

Title

Sputum differential cell counts

Description

Changes in sputum differential cell counts

Time Frame

Day 1, Day 30, Day 59 and Day 89

Title

PC20

Description

Changes in methacholine PC20

Time Frame

Day 1, Day 30. Day 59 and Day 89

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Aged ≥18 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. Significant other primary pulmonary disorders in particularly; pulmonary embolism, pulmonary hypertension, interstitial lung disease, lung cancer, cystic fibrosis, emphysema or bronchiectasis. Pregnancy or breast-feeding Use of ACE (angiotensin converting enzyme) inhibitors Any centrally acting medication which in the view of the investigator could alter the sensitivity of the cough reflex History of psychiatric illness, drug or alcohol abuse which may interfere in the participation of the trial.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gail Gauvreau, PhD

Organizational Affiliation

McMaster University

Official's Role

Principal Investigator

Facility Information:

Facility Name

McMaster Cardio-Respiratory Research Lab

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L8N 3Z5

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34192396

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.

Results Reference

derived

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Probiotics and Capsaicin Evoked Coughs

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