Influence on Cough and Airway Symptoms by Oral Capsaicin
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|ClinicalTrials.gov Identifier: NCT04125563|
Recruitment Status : Recruiting
First Posted : October 14, 2019
Last Update Posted : October 8, 2020
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.
- 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
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
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.
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.
|Condition or disease||Intervention/treatment||Phase|
|Cough||Drug: Capsicum Oleoresin Drug: Placebos||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||Randomised, crossover, double blind|
|Masking:||Single (Outcomes Assessor)|
|Masking Description:||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.|
|Official Title:||Influence on Cough and Airway Symptoms by Oral Capsaicin - a Phase 2, Randomised, Placebo-controlled Clinical Study in Patients With Chronic Idiopathic Cough|
|Actual Study Start Date :||June 1, 2019|
|Estimated Primary Completion Date :||June 8, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Placebo Comparator: Placebo capsules
Soft gel capsules with placebo: Sorbitol and colorant.
Soft gel capsules filled with placebo - sorbitol and colorant.
Active Comparator: 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.
Drug: Capsicum Oleoresin
The soft gel capsules used in the study are easily digested in the stomach and contain standardised doses of 0,4 mg Capsicum oleoresin with the main component capsaicin (8-methyl-N-vanillyl-6-nonenamide) (from chili extract).
Other Name: Capsaicin
- Capsaicin cough sensitivity [ Time Frame: 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
- Cough monitor recordings [ Time Frame: From baseline up to 4 weeks post-treatment. ]Objectively measured cough counting (LCM) at four opportunities. Change from baseline at the end of four weeks of treatment with active substance or placebo.
- Visual analogue scale (VAS-scale) [ Time Frame: From baseline up to 4 weeks post-treatment. ]
At each visit: Using the VAS-scale evaluating 6 symptoms; cough, rhinitis, throat irritation, dyspnoea, stomach problems and urinary incontinence are recorded on a VAS-scale of 0 to 100 mm, with 0 indicating no symptoms and 100 indicating intense symptoms. The patients put an X on a line of exactly 100 millimeters. The nurse then measures the length from the beginning of the line to the X and register this in the case report form. There are no subscores. The patients are told that an X on the line's beginning indicates no symptoms at all and an X at the line's ending indicates worse possible symptoms.
Change from baseline to each of the four weeks of treatment with active substance and placebo. The procedure takes about 5 minutes. The analyses for all patients will be performed when the entire study is completed.
- Height [ Time Frame: From baseline up to 4 weeks post-treatment. ]At study start the patient's height is recorded in meters.
- Weight [ Time Frame: From baseline up to 4 weeks post-treatment. ]At each visit the patient's weight in kilograms will be recorded.
- BMI - Body Mass Index. Weight and height will be combined to report BMI in kg/m2. [ Time Frame: From baseline up to 4 weeks post-treatment. ]At each visit the patient's weight in kilograms will be recorded and aggregated with the height measured at baseline to calculate BMI in kg/m2.
- Lung function: Forced expiratory volume (liters) in one second (FEV1). [ Time Frame: From baseline up to 4 weeks post-treatment. ]At each visit the FEV1 is measured (and predicted values of FEV1 according to gender, age and body length) using the Masterscope spirometer (Masterscope, APS version 5.02 software). After a maximal inhalation a forced exhalation during one second is recorded.
- Lung function: Predicted value (%) of Forced expiratory volume (liters) in one second (FEV1). [ Time Frame: From baseline up to 4 weeks post-treatment. ]At each visit the predicted values of FEV1 according to gender, age and body length) will be calculated using the Masterscope spirometer (Masterscope, APS version 5.02 software). After a maximal inhalation a forced exhalation during one second is recorded.
- Lung function: Forced vital capacity (FVC) (liters). [ Time Frame: From baseline up to 4 weeks post-treatment. ]At each visit the FVC is measured using the Masterscope spirometer (Masterscope, APS version 5.02 software). The FVC is calculated after maximal inhalation followed by a forced maximal exhalation.
- Lung function: FEV% [ Time Frame: From baseline up to 4 weeks post-treatment. ]At each visit FEV% is measured. FEV% is defined as FEV1/VC and is thus a measure of how much of her/his vital capacity the patient exhales during the first second of a forced expiration.
- Lung function: Impulse oscillometry (IOS) (Resistance - Hz) [ Time Frame: From baseline up to 4 weeks post-treatment. ]At each visit after the spirometry is assessed lung function is also measured with impulse oscillometry (IOS) to record airway resistance at 5 and 20 hertz and to measure the area under the curve (Ax) mirroring the resistance in the peripheral airways using Jaeger Masterscope IOS™. After this the participants inhale bronchodilator medication and 15 minutes thereafter perform an additional lung function test. This is a standard procedure for examining lung function.
- Lung function: Fractional exhaled nitric oxide (FeNO) [ Time Frame: From baseline up to 4 weeks post-treatment. ]At 4 visits lung function is also evaluated with measurements of fractional exhaled nitric oxide (FeNO) in accordance with international American Thoracic Society/ERS recommendations, using a NIOX, nitric oxide gas analyser (Aerocrine AB, Stockholm, Sweden).
- Cough sensitivity to inhaled capsaicin - to reach 10 coughs [ Time Frame: From baseline up to 4 weeks post-treatment. ]At each visit: LogC10 (logarithmic values of the inhaled capsaicin threshold concentration needed to reach 10 coughs) (C10)). Change from baseline at the end of two and four weeks of treatment with active substance or placebo.
- Examination of the amount, weight and composition of particles in exhaled air by the PExA method. [ Time Frame: From baseline up to 4 weeks post-treatment. ]At each visit: Evaluating possible chemical changes in the small airways by collecting particles in the exhaled air with a non-invasive method using the PExA 2.0 (PExA AB, Gothenburg, Sweden). After capsaicin provocation and lung function measurements exhaled particles are measured with White FHLC Membrane Filter Type: 0.45mm and then frozen for later analyses.
- The Swedish version of the Hull Airway Reflux Questionnaire (HARQ-S) [ Time Frame: From baseline up to 4 weeks post-treatment. ]At each visit: The Hull Airway Reflux Questionnaire (HARQ) was developed with the aim of eliciting the major component of chronic cough in adults. It comprises 14 items with a maximum total score of 70. A Swedish version (HARQ-S) has previously been validated. A total score of <13 points is regarded as normal while higher scores indicate more symptoms and problems of chronic cough.
- The Swedish version of the Leicester Cough Questionnaire (LCQ-S) [ Time Frame: From baseline up to 4 weeks post-treatment. ]At each visit: The validated LCQ-S is a self-reporting quality of life measure of chronic cough for adults. It consists of 19 items with a 7-point response scale (range from 1 to 7). Each item is developed to assess symptoms during cough and impact of cough on three main domains: physical, psychological and social. Scores are calculated as a mean of each domain and total score is calculated by adding every domain score.
- Pain sensitivity with pressure algometry (PPT) [ Time Frame: From baseline up to 4 weeks post-treatment. ]At each visit: Pain sensitivity is evaluated by pressure pain thresholds for measuring and quantifying deep tenderness in muscles. The Somedic algometer (SBMEDIC Electronics, Solna, Sweden) is a gun-shaped handle creating pressure through a pressure sensitive strain gauge at the tip, connected to a power supply, an amplifier and a display unit. The display shows the actual pressure given (kPa/s), and a scale indicates the rate of pressure to help the examiner to keep the pressure constant.
- Chest mobility [ Time Frame: From baseline up to 4 weeks post-treatment. ]At each visit: Chest mobility (in cm) is assessed with a tape measure as chest expansion, thoracic flexion and extension. Chest expansion is measured as the circumference difference after maximal inhalation through the nose and maximal exhalation through the mouth at the level of the xiphoid process with participants in a standing position with their hands on their head. Thoracic flexion and thoracic extension are measured 30 cm distally from the seventh cervical vertebrae (C7) in a standing position with the patient's hands along their sides. Every measurement is performed three times, and the best of the three measurements is noted.
- Serum analyses of capsaicin and dihydrocapsaicin [ Time Frame: From baseline up to 4 weeks post-treatment. ]
At each visits samples are taken for serum analyses with high performance liquid chromatography (HPLC) in accordance with Hartley et al:
"Total capsaicinoids are extracted from 1 mL aliquots of serum or plasma using methyl-isobutyl ketone, evaporation of the extract to dryness and reconstitution with 200 microliter of acetonitrile. The HPLC mobile phase is 40:60 water:acetonitrile. The absorbance of the eluent is monitored at 205 nm. Inter batch reproducibility for both is 15%. The limits of detection are 2.6 and 3.8 ng/mL for capsaicin and dihydrocapsaicin respectively." Also see reference.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04125563
|Contact: Eva Millqvist, MD, PhDemail@example.com|
|Contact: Ewa Ternesten-Hasseus, RN, PhDfirstname.lastname@example.org|
|Allergy clinic, Sahlgrenska University Hospital||Recruiting|
|Gothenburg, Vastra Gotaland Region, Sweden, 413 45|
|Contact: Eva Millqvist, MD, PhD +46708433819 email@example.com|
|Contact: Ewa Ternesten-Hasseus, RN, PhD +46703418909 firstname.lastname@example.org|
|Principal Investigator:||Eva Millqvist, MD, PhD||Vastra Gotaland Region|