Influence on Cough and Airway Symptoms by Oral Capsaicin - a Phase 2, Randomised, Placebo-controlled Clinical Study in Patients With Chronic Idiopathic Cough
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 55
- 试验地点
- 2
- 主要终点
- Capsaicin cough sensitivity
研究概览
简要总结
Study objectives
To establish whether an oral intake of Capsicum oleoresin; capsaicinoids expressed as 0.4 mg capsaicin (C18H27N03; Mw: 305.4) in each capsule (from chili extract) can desensitise the cough reflex and improve unexplained coughing.
Study period
- Estimated Start date (first patient enrolled) June 2019
- Estimated End date (last patient completed follow up) June 2020
- First data available for presentation September 2020
Investigational product/comparator
The formulation is prepared from Capsicum oleoresin. Each capsule will contend a dose corresponding to 0.4 mg capsaicin. All test methods are as per the European Pharmacopoeia for Capsicum oleoresin refined and standardised.
- The formulation is developed by Research Institutes of Sweden (RISE), Sodertalje, Sweden
- Supplier of raw material for the Capsicum oleoresin product/IMP: RANSOM; Ltd, London, UK
- Producer of capsules with Capsicum oleoresin and placebo: by Catalent Pharma Solutions, St Petersburg, Florida, USA
- Packing bottles of capsules with the investigational medical product (IMP) and placebo: by Apotek Produktion & Laboratorier AB (APL), Stockholm, Sweden
Study design
Capsules, taken orally, with standardised doses of Capsicum oleoresin corresponding to 0.4 mg pure capsaicin (from chili extract) in each capsule in comparison to matched capsules with placebo (sorbitol and colorant), all capsules looking the same. Four weeks of active treatment is compared to four weeks of placebo. In between there is a wash out period of two weeks.
The time frame is 24 hours + 10 weeks. During the first 24 hours the patients carry a cough recorder (Leicester Cough Monitor - LCM) and then start with 4 weeks of active treatment or placebo. This is followed by 2 weeks of wash out and then the patients start with another 4 weeks of active treatment or placebo. After this the study ends.
Collaboration
Professor Alyn Morice MD, PhD, chief physician at Hull York Medical School, University of Hull, UK. Professor Surinder Birring MD, Senior Lecturer, specialist in respiratory medicine, Imperial College, London, UK. Associate professor Alastair Ross,PhD, Chalmers University of Technology, Gothenburg, Sweden.
Study center and number of subjects planned
All clinical trials take place at the asthma and allergy clinic, Sahlgrenska University Hospital, Gothenburg, Sweden from where 60 patients with chronic idiopathic cough (CIC) are recruited.
详细描述
This is a phase 2 clinical study in humans for therapeutic use of Capsicum oleoresin - (capsaicin) in chronic idiopathic cough (CIC). The study has a randomised, double-blind and cross-over design. During 4 weeks the participants take either active capsules (Capsicum oleoresin), or matching placebo capsules. This period follows by 2 weeks of "wash out" and then another 4 weeks with active capsules or placebo.
The IMP
The soft gel capsules used in the study are easily digested in the stomach and contain standardised doses of Capsicum oleoresin with the main component capsaicin (8-methyl-N-vanillyl-6-nonenamide) (from chili extract). The placebo capsules are filled with sorbitol and colorant.
Capsicum oleoresin and capsaicin is found naturally in a variety of chili fruits and the use of chili peppers in food varies greatly between different parts of the world. The maximum daily intake of capsaicin from Capsicum oleoresin in the current study could be exceeded many times in countries such as Mexico and Thailand, but it does not reach that level in most Western countries.
In concordance with the known effect of topical capsaicin for neuropathic pain, the expected effect of orally taken capsaicin is desensitisation. Capsaicin desensitise the cough-sensitive transient receptor potential vanilloids one receptors (TRPV1) and other TRP receptors followed by decreased cough reflex sensitivity and coughing in patients with CIC. Capsaicin causes depletion of neuropeptides leading to "exhausting" of the receptor with ameliorated symptoms in the patients.
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
- Single (Outcomes Assessor)
盲法说明
Capsules, taken orally, with standardised doses of Capsicum oleoresin corresponding to 0.4 mg pure capsaicin (from chili extract) in each capsule, will be compared to matched capsules with placebo, all capsules looking the same.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Out-patients, men and women
- •Age 18-75 years
- •Present non-smoker
- •A diagnosis of CIC, set by a trained specialised physician
- •Exceeding the cut off limit for the Swedish version of the Hull Airway Reflux Questionnaire (HARQ-S): (a total score of ≥13 points)
- •At screening visit reporting daily, troublesome coughing and an easily evoked cough reflex since at least two months
- •At screening visit having a positive capsaicin inhalation cough test
排除标准
- •Known or suspected chili allergy
- •Known or suspected allergy to the colorant Tartrazine (FD&C Yellow #6)
- •Any kind of diabetes
- •Treatment the preceding month with any kind of chili medication or food supplement containing capsaicin or having a diet including chili in treatment purpose
- •Treatment the preceding month with medication according to the study protocol
- •Pregnancy, breast-feeding, planned pregnancy during the study and fertile women not using acceptable contraceptive measures, as judged by the investigator
- •Suspected poor capability to follow instructions of the study, e.g. because of a history of drug abuse, difficult to read and/or understand Swedish or any other reason, as judged by the investigator
- •Airway infection the last 4 weeks before study start
- •Any significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or influence the results of the study, or the patient's ability to participate in the study
- •Any clinically relevant abnormal findings in physical examination, vital signs at baseline visit, which, in the opinion of the investigator, may put the patient at risk because of his/her participation in the study
- •Previous randomisation of treatment in the present study
- •Participation in another clinical study 30 days prior to and during this study
- •Smoking during the last ten years or/and >10 pack years
- •Known alcohol and/or drug abuse
- •The participants will be asked for any season allergy or other allergy and for allergen exposure. The study start date will be adjusted to season or another possible allergen exposure.
研究组 & 干预措施
Placebo capsules
Soft gel capsules with placebo: Sorbitol and colorant.
干预措施: Placebos (Drug)
Active substance - oral capsaicin in soft gel capsules
This is a phase 2 clinical study in humans for therapeutic use of Capsicum oleoresin - (capsaicin) in CIC. The study has a randomised, double-blind and cross-over design. During 4 weeks the participants take either active capsules (Capsicum oleoresin), or matching placebo capsules. This period follows by 2 weeks of "wash out" and then another 4 weeks with active capsules or placebo in accordance with the trial profile below.
干预措施: Capsicum Oleoresin (Drug)
结局指标
主要结局
Capsaicin cough sensitivity
时间窗: From baseline up to 4 weeks post-treatment.
The primary efficacy variables will be capsaicin inhalation cough sensitivity at each visit in terms of: * LogC2 (logarithmic values of the inhaled capsaicin threshold concentration needed to reach two coughs (C2)). Change from baseline at the end of two and four weeks of treatment with active substance or placebo * LogC5 (logarithmic values of the inhaled capsaicin threshold concentration needed to reach five coughs (C5)). Change from baseline at the end of two and four weeks of treatment with active substance or placebo
次要结局
- Cough monitor recordings(From baseline up to 4 weeks post-treatment.)
- Visual analogue scale (VAS-scale)(From baseline up to 4 weeks post-treatment.)