Probiotics and Capsaicin Evoked Coughs

NCT ID: NCT03603522

Last Updated: 2021-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-16
• Study Completion Date: 2021-01-18

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.

Conditions

Atopic Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

BioGaia-DSM17938

Intervention Type: DIETARY_SUPPLEMENT

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

Placebo Comparator: Placebo Control

Intervention Type: OTHER

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

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.

Group Type: PLACEBO_COMPARATOR

BioGaia-DSM17938

Intervention Type: DIETARY_SUPPLEMENT

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

Placebo Comparator: Placebo Control

Intervention Type: OTHER

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

Interventions

BioGaia-DSM17938

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

Intervention Type: DIETARY_SUPPLEMENT

Placebo Comparator: Placebo Control

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

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioGaia AB

INDUSTRY

Sponsor Role: collaborator

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gail Gauvreau, PhD

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

McMaster Cardio-Respiratory Research Lab

Hamilton, Ontario, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 34192396 (View on PubMed)

Other Identifiers

McMaster- DSM17938-5095

Identifier Type: -

Identifier Source: org_study_id