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

NCT06960759 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-0206
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Chronic Cough (CC); Refractory Chronic Cough; Unexplained Chronic Cough

Keywords

cough hypersensitivity syndrome; randomized control trial; neurogenic cough; refractory chronic cough; unexplained chronic cough; chronic cough; behavioral cough suppression therapy

Outcome Measures

Primary Outcomes (4)

• Cough threshold sensory testing (CTT)

  Measure of cough sensitivity using progressive doses of inhaled vaporized citric acid. The dose causing 5 or more coughs (C5) is the endpoint.

  From enrollment to 14 weeks following enrollment

• Cough suppression threshold testing (CSTT)

  Measure of cough suppression ability using progressive doses of inhaled vaporized citric acid. The dose causing 5 or more coughs when trying to not cough (CS5) is the endpoint.

  From enrollment to 14 weeks following enrollment

• Urge-to-Cough Sensory Motor Threshold Difference (UTC S-M Thresh Diff)

  A measure of the relationship between sensation of UTC and motor action of coughing. The measure is determined by calculating the difference between first UTC felt during cough threshold testing (Cu) and UTC at the dose of citric acid that causes 2 or more coughs (C2) (i.e., UTC at C2 - UTC at Cu).

  From enrollment to 14 weeks following enrollment

• Blood oxygen level dependent neural responses (BOLD)

  Whole-brain fMRI performed during inhalation of capsaicin to trigger urge-to-cough. (NOTE: this measure is only required for those enrolling at Univ. of Colorado)

  From enrollment to 14 weeks following enrollment

Secondary Outcomes (2)

• Leicester Cough Questionnaire (LCQ)

  From enrollment to 23 weeks following enrollment

• Cough frequency

  From enrollment to 14 weeks following enrollment

Study Arms (3)

Behavioral treatment plus inactive drug

ACTIVE COMPARATOR

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

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

Behavioral treatment plus inhaled drug

EXPERIMENTAL

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

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

Inhaled drug

EXPERIMENTAL

Participants inhale a drug designed to desensitize the cough reflex.

Drug: Inhaled capsaicin (CAP)

Interventions

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

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

Behavioral treatment plus inactive drug

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

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

Behavioral treatment plus inhaled drug

Inhaled capsaicin (CAP) DRUG

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

Inhaled drug

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Montana: lead
• University of Colorado, Denver: collaborator
• Emory University: collaborator
• University of Melbourne: collaborator

Study Sites (3)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Montana

Missoula, Montana, 59812, United States

Location

Related Publications (5)

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

  PMID: 3602068 BACKGROUND

• 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.

  PMID: 38244293 BACKGROUND

• 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.

  PMID: 37118696 BACKGROUND

• 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.

  PMID: 35091204 BACKGROUND

• 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.

  PMID: 25787221 BACKGROUND

MeSH Terms

Conditions

Chronic Cough; cough hypersensitivity syndrome

Condition Hierarchy (Ancestors)

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

Study Officials

• Laurie J Slovarp, PhD

  University of Montana

  PRINCIPAL INVESTIGATOR

• Marie Jetté, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laurie J Slovarp, PhD

CONTACT

406-243-2107; laurie.slovarp@umontana.edu

Marie Jetté, PhD

CONTACT

marie.jette@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 28, 2025
• First Posted: May 7, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): March 31, 2030
• Last Updated: May 11, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (3)