Influence on Cough and Airway Symptoms by Oral Capsaicin

NCT04125563 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 2016-004463-39
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cough

Keywords

Cough hypersensitivity syndrome; Capsaicin cough sensitivity; Cough monitor

Outcome Measures

Primary Outcomes (1)

• Capsaicin cough sensitivity

  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

  From baseline up to 4 weeks post-treatment.

Secondary Outcomes (2)

• Cough monitor recordings

  From baseline up to 4 weeks post-treatment.

• Visual analogue scale (VAS-scale)

  From baseline up to 4 weeks post-treatment.

Other Outcomes (16)

• Height

  From baseline up to 4 weeks post-treatment.

• Weight

  From baseline up to 4 weeks post-treatment.

• BMI - Body Mass Index. Weight and height will be combined to report BMI in kg/m2.

  From baseline up to 4 weeks post-treatment.

Study Arms (2)

Placebo capsules

PLACEBO COMPARATOR

Soft gel capsules with placebo: Sorbitol and colorant.

Drug: Placebos

Active substance - oral capsaicin in soft gel capsules

ACTIVE COMPARATOR

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

Interventions

Capsicum Oleoresin DRUG

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).

Also known as: Capsaicin

Active substance - oral capsaicin in soft gel capsules

Placebos DRUG

Soft gel capsules filled with placebo - sorbitol and colorant.

Placebo capsules

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vastra Gotaland Region: lead
• Sahlgrenska University Hospital: collaborator
• Vinnova: collaborator

Study Sites (1)

Allergy clinic, Sahlgrenska University Hospital

Gothenburg, Västra Götaland County, 413 45, Sweden

Location

Related Publications (6)

• Ternesten-Hasseus E, Johansson EL, Millqvist E. Cough reduction using capsaicin. Respir Med. 2015 Jan;109(1):27-37. doi: 10.1016/j.rmed.2014.11.001. Epub 2014 Nov 12.

  PMID: 25468411 BACKGROUND

• Pullerits T, Ternesten-Hasseus E, Johansson EL, Millqvist E. Capsaicin cough threshold test in diagnostics. Respir Med. 2014 Sep;108(9):1371-6. doi: 10.1016/j.rmed.2014.07.012. Epub 2014 Aug 4.

  PMID: 25129869 BACKGROUND

• Hartley T, Stevens B, Ahuja KD, Ball MJ. Development and experimental application of an HPLC procedure for the determination of capsaicin and dihydrocapsaicin in serum samples from human subjects. Indian J Clin Biochem. 2013 Oct;28(4):329-35. doi: 10.1007/s12291-013-0297-0. Epub 2013 Jan 20.

  PMID: 24426233 BACKGROUND

• Johansson EL, Ternesten-Hasseus E, Olsen MF, Millqvist E. Respiratory movement and pain thresholds in airway environmental sensitivity, asthma and COPD. Respir Med. 2012 Jul;106(7):1006-13. doi: 10.1016/j.rmed.2012.03.011. Epub 2012 Apr 15.

  PMID: 22510540 BACKGROUND

• Sonnerfors P, Faager G, Einarsson U. Translation of the Leicester Cough Questionnaire into Swedish, and validity and reliability in chronic obstructive pulmonary disease. Disabil Rehabil. 2018 Nov;40(22):2662-2670. doi: 10.1080/09638288.2017.1353648. Epub 2017 Jul 20.

  PMID: 28728439 BACKGROUND

• Johansson EL, Ternesten-Hasseus E. Reliability and Validity of the Swedish Version of the Hull Airway Reflux Questionnaire (HARQ-S). Lung. 2016 Dec;194(6):997-1005. doi: 10.1007/s00408-016-9937-5. Epub 2016 Sep 16.

  PMID: 27638152 BACKGROUND

MeSH Terms

Conditions

Cough; cough hypersensitivity syndrome

Interventions

oleoresins; Capsaicin

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Polyunsaturated Alkamides; Amides; Organic Chemicals; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids

Study Officials

• Eva Millqvist, MD, PhD

  Vastra Gotaland Region

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Randomised, crossover, double blind

Study Record Dates

• First Submitted: September 2, 2019
• First Posted: October 14, 2019
• Study Start: June 1, 2019
• Primary Completion: December 30, 2025
• Study Completion (Estimated): June 15, 2026
• Last Updated: November 25, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)