Atopic Asthma
Conditions
Keywords
Cough, Capsaicin, Probiotics, TRPV1
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.
Interventions
DIETARY_SUPPLEMENTBioGaia-DSM17938
2mL per day (1x10\^9 CFU) per day taken orally for 28 days
2mL per day of placebo formulation taken orally for 28 days
Sponsors
BioGaia AB
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Emax | Day 1, Day 30, Day 59 and Day 89 | The maximum number of capsaicin evoked coughs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose response | Day 1, Day 30, Day 59 and Day 89 | Changes in the capsaicin full dose response curves |
| 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) |
| Responses to histamine | Day 1, Day 30, Day 59 and Day 89 | The wheal responses to graded doses of histamine skin prick testing |
| 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 |
| T-Cell Cytokine | Day 1, Day 30, Day 59 and Day 89 | Inhibition of T-Cell cytokine responses to stimulation in blood |
| 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 |
| 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) |
Countries
Canada
Outcome results
None listed