Mechanisms of Change in Behavioral Cough Suppression Therapy for Refractory Chronic Cough

NCT ID: NCT06960759

Last Updated: 2025-05-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-08-01

Study Completion Date

2030-03-31

Brief Summary

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This study is testing new ways to help people who have chronic cough that has not improved with typical treatments. One approach is called behavioral cough suppression (BCS) therapy, which teaches people techniques to stop themselves from coughing. Another approach uses capsaicin, the substance that makes chili peppers hot, to help reduce the body's sensitivity to cough triggers.

In this study, we will test three treatments:

* BCS therapy with capsaicin (BCS+CAP),
* BCS therapy with a placebo (BCS+Sham),
* Capsaicin stimulation alone (CAP).

The investigators will enroll 150 adults with chronic cough and randomly assign them to one of the three treatments. Each person will attend 12 treatment sessions.

The investigators want to find out how these treatments affect:

* How sensitive someone is to things that make them cough,
* How well they can hold back a cough when they try,
* How their brain responds to things that cause an urge-to-cough,
* And how much their coughing affects their quality of life.

The investigators believe all treatments may reduce sensitivity to cough stimulants, but BCS treatments will also improve how people sense and control the urge to cough. The investigators think combining BCS with capsaicin will work the best overall.

Detailed Description

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Refractory chronic cough (RCC) is a persistent and costly condition that is difficult to treat, often persisting despite appropriate treatment of underlying causes. While behavioral cough suppression (BCS) therapy has shown effectiveness in reducing cough frequency and improving quality of life in controlled studies, it remains underutilized, and the mechanisms by which it works are not well understood.

This multi-site randomized controlled trial will investigate the effects and mechanisms of BCS therapy with and without the addition of capsaicin desensitization, compared to capsaicin stimulation alone. Capsaicin, a known cough stimulant, has demonstrated desensitization effects on sensory pathways in conditions such as chronic rhinitis and pain syndromes, suggesting potential utility in modulating cough-related neural pathways.

The investigators will recruit 150 participants diagnosed with RCC and randomize them into one of three treatment arms:

* BCS combined with capsaicin stimulation (BCS+CAP),
* BCS combined with sham stimulation (BCS+Sham),
* Capsaicin stimulation alone (CAP).

Participants will undergo 12 treatment sessions over several weeks. The study will evaluate both behavioral and neural markers of treatment response. Primary outcome measures will include:

* Cough sensory threshold (C5): the lowest concentration of citric acid causing five or more coughs,
* Cough suppression ability: the ability to suppress cough when instructed (the difference between the dose of capsaicin causing five or more coughs when trying to suppress cough (CS5) and C5,
* Urge-to-cough (UTC) sensory-motor threshold difference: a measure of how perception of the need to cough relates to actual coughing behavior,
* Blood oxygen level dependent (BOLD) neural responses using whole-brain functional MRI (fMRI) during UTC stimulation.

Secondary outcomes will include patient-reported measures such as the Leicester Cough Questionnaire (LCQ) and objective ambulatory cough frequency monitoring.

The investigators hypothesize that all three treatments will lead to desensitization of cough sensitivity (i.e., increase in C5), but only the BCS-based interventions will alter UTC thresholds, suppression ability, and brain network activity. We further hypothesize that the combination of BCS and capsaicin (BCS+CAP) will provide the greatest therapeutic benefit due to simultaneous peripheral desensitization and central sensory-motor modulation.

Conditions

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Chronic Cough (CC) Refractory Chronic Cough Unexplained Chronic Cough

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Behavioral treatment plus inactive drug

Participants receive behavioral cough suppression therapy (BCST) combined with an inactive inhaled substance.

Group Type ACTIVE_COMPARATOR

Behavioral cough suppression therapy combined with inactive inhaled drug (BCS+Sham)

Intervention Type BEHAVIORAL

Behavioral cough suppression therapy plus inactive inhaled drug. Treatment given twice per week for 12 sessions.

Behavioral treatment plus inhaled drug

Participants receive behavioral cough suppression therapy (BCST) combined with inhaled vaporized drug designed to enhance BCST

Group Type EXPERIMENTAL

Behavioral cough suppression therapy combined with capsaicin inhalation (BCS+CAP)

Intervention Type COMBINATION_PRODUCT

Behavioral cough suppression therapy combined with inhaled capsaicin (cough stimulant). Treatment given twice per week for 12 sessions.

Inhaled drug

Participants inhale a drug designed to desensitize the cough reflex.

Group Type EXPERIMENTAL

Inhaled capsaicin (CAP)

Intervention Type DRUG

Repeated inhalation of diluted capsaicin in increasing concentrations. Treatment given twice per week for 12 sessions.

Interventions

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Behavioral cough suppression therapy combined with inactive inhaled drug (BCS+Sham)

Behavioral cough suppression therapy plus inactive inhaled drug. Treatment given twice per week for 12 sessions.

Intervention Type BEHAVIORAL

Behavioral cough suppression therapy combined with capsaicin inhalation (BCS+CAP)

Behavioral cough suppression therapy combined with inhaled capsaicin (cough stimulant). Treatment given twice per week for 12 sessions.

Intervention Type COMBINATION_PRODUCT

Inhaled capsaicin (CAP)

Repeated inhalation of diluted capsaicin in increasing concentrations. Treatment given twice per week for 12 sessions.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of refractory or unexplained chronic cough
* Normal chest x-ray within past 2 years, without change in cough symptoms
* If diagnosed with asthma, is it well controlled
* Normal spirometry (or FEV1/FVC of at least 70% if diagnosed with asthma) within two years, without change in symptoms since
* Laryngoscopy or stroboscopy within 2 years without evidence of structural pathology and no change in vocal quality since exam
* Proficient reader/speaker of English
* Willing to take a pregnancy test before enrollment (if applicable)
* Willing to use contraception during the study (if applicable)
* Demonstrates understanding in study procedures and risks in order to consent

Exclusion Criteria

* Currently a smoker of any substance
* Currently suffering from any signs of an upper respiratory infection (other than cough)
* Hemoptysis (coughing up blood)
* Pulmonary diagnosis other than asthma
* Used an ACE-inhibitor in the past 60 days
* Pregnant or trying to become pregnant
* Any complaints or clinical symptoms of dysphagia
* Live with or work with anyone with chronic cough


* Presence of metal implants, devices or fragments in the body
* Claustrophobia
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Colorado, Denver

OTHER

Sponsor Role collaborator

Emory University

OTHER

Sponsor Role collaborator

University of Melbourne

OTHER

Sponsor Role collaborator

University of Montana

OTHER

Sponsor Role lead

Responsible Party

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Laurie Slovarp

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Laurie J Slovarp, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Montana

Marie Jetté, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

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University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

University of Montana

Missoula, Montana, United States

Site Status

Countries

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United States

Central Contacts

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Laurie J Slovarp, PhD

Role: CONTACT

406-243-2107

Marie Jetté, PhD

Role: CONTACT

Facility Contacts

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Marie Jetté, PhD

Role: primary

303-724-3918

Amanda Gillespie, PhD

Role: primary

404-778-3381

Laurie J Slovarp, PhD

Role: primary

406-243-2107

References

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Losche D, Furst W, Falk M, Weickert H. [Preparation of a cytostatic-containing bone cement]. Pharmazie. 1987 Feb;42(2):97-9. German.

Reference Type BACKGROUND
PMID: 3602068 (View on PubMed)

Moe AAK, Singh N, Dimmock M, Cox K, McGarvey L, Chung KF, McGovern AE, McMahon M, Richards AL, Farrell MJ, Mazzone SB. Brainstem processing of cough sensory inputs in chronic cough hypersensitivity. EBioMedicine. 2024 Feb;100:104976. doi: 10.1016/j.ebiom.2024.104976. Epub 2024 Jan 19.

Reference Type BACKGROUND
PMID: 38244293 (View on PubMed)

Slovarp LJ, Reynolds JE, Tolbert S, Campbell S, Welby S, Morkrid P. Cough desensitization treatment for patients with refractory chronic cough: results of a second pilot randomized control trial. BMC Pulm Med. 2023 Apr 28;23(1):148. doi: 10.1186/s12890-023-02423-6.

Reference Type BACKGROUND
PMID: 37118696 (View on PubMed)

Slovarp L, Reynolds JE, Bozarth-Dailey E, Popp S, Campbell S, Morkrid P. Cough desensitization treatment: A randomized, sham-controlled pilot trial for patients with refractory chronic cough. Respir Med. 2022 Mar;193:106739. doi: 10.1016/j.rmed.2022.106739. Epub 2022 Jan 15.

Reference Type BACKGROUND
PMID: 35091204 (View on PubMed)

Chamberlain SA, Garrod R, Douiri A, Masefield S, Powell P, Bucher C, Pandyan A, Morice AH, Birring SS. The impact of chronic cough: a cross-sectional European survey. Lung. 2015 Jun;193(3):401-8. doi: 10.1007/s00408-015-9701-2. Epub 2015 Mar 19.

Reference Type BACKGROUND
PMID: 25787221 (View on PubMed)

Other Identifiers

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25-0206

Identifier Type: -

Identifier Source: org_study_id

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