Probiotics and Capsaicin Evoked Coughs

Atopic Asthma Clinical Trial

— PCEC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03603522
• Other study ID #: McMaster- DSM17938-5095
• Status: Completed
• Phase: N/A
• Start date: July 16, 2019
• Est. completion date: January 18, 2021

Study information

• Verified date: March 2019
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: January 18, 2021
• Est. primary completion date: January 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atopic Asthma
• Cough

Intervention

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

Locations

Country	Name	City	State
Canada	McMaster Cardio-Respiratory Research Lab	Hamilton	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
McMaster University	BioGaia AB

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Emax	The maximum number of capsaicin evoked coughs	Day 1, Day 30, Day 59 and Day 89
Secondary	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
Secondary	Dose response	Changes in the capsaicin full dose response curves	Day 1, Day 30, Day 59 and Day 89
Secondary	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
Secondary	Responses to histamine	The wheal responses to graded doses of histamine skin prick testing	Day 1, Day 30, Day 59 and Day 89
Secondary	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
Secondary	T-Cell Cytokine	Inhibition of T-Cell cytokine responses to stimulation in blood	Day 1, Day 30, Day 59 and Day 89
Secondary	Sputum differential cell counts	Changes in sputum differential cell counts	Day 1, Day 30, Day 59 and Day 89
Secondary	PC20	Changes in methacholine PC20	Day 1, Day 30. Day 59 and Day 89