A Double-Blind Randomized Placebo Controlled Trial Investigating the Effects of DSM17938 on Capsaicin Evoked Coughs
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Emax
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
结局指标
主要结局
Emax
时间窗: Day 1, Day 30, Day 59 and Day 89
The maximum number of capsaicin evoked coughs
次要结局
- ED50 (median effective dose)(Day 1, Day 30, Day 59 and Day 89)
- C2 and C5(Day 1, Day 30, Day 59 and Day 89)
- T-Cell Cytokine(Day 1, Day 30, Day 59 and Day 89)
- Itch Intensity(Day 1, Day 30, Day 59 and Day 89)
- Dose response(Day 1, Day 30, Day 59 and Day 89)
- Responses to histamine(Day 1, Day 30, Day 59 and Day 89)
- Sputum differential cell counts(Day 1, Day 30, Day 59 and Day 89)
- PC20(Day 1, Day 30. Day 59 and Day 89)