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: 135
• 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 a natural substance thought to help reduce the body's sensitivity to cough triggers. In this study, we will test two treatments and include one no-treatment control group. The control group will undergo baseline testing, cough monitoring, and an fMRI brain scan and will be offered BCS at end of study participation. The two treatments include:

• BCS therapy with active inhaled treatment (BCS+active),
• BCS therapy with inactive inhaled treatment (BCS+inactive), The investigators will enroll 135 adults with refractory chronic cough (RCC). 100 participants who qualify and are willing and able to complete 14 study visits in the clinic and two online study visits will be randomly assigned to one of the two treatments. The no-treatment control group (n=35) will be recruited from adults with RCC who are willing to complete baseline testing and fMRI but are not able or willing to attend 14 study clinic visits. These participants will not be randomized. 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 both treatments will reduce sensitivity to cough stimulants, reduce cough severity, and improve quality of life, but BCS+active inhaled treatment will work better than BCS+inactive inhaled treatment.

Conditions

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

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 4 weeks following enrollment

• Cough suppression threshold difference (CS Thresh Diff)

  Measure of cough suppression ability. The participant first completes cough suppression threshold testing which involves inhalation of progressive doses of citric acid while actively trying to suppress cough. The dose causing 5 or more coughs when trying to not cough (CS5) is the endpoint. CS Thresh Diff is the difference between CS5 and C5.

  From enrollment to 4 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 4 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)

  4 weeks following enrollment BCS+CAP and BCS+Sham participants; enrollment to 1 week post-enrollment for the fMRI control group

Secondary Outcomes (10)

• Leicester Cough Questionnaire (LCQ)

  From enrollment to 19 weeks following enrollment

• Cough frequency

  From enrollment to 11 weeks following enrollment

• Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ)

  From enrollment to 19 weeks following enrollment

• Voice Handicap Index - 10 (VHI-10)

  From enrollment to 19 weeks following enrollment

• Multidimensional Assessment of Interoceptive Awareness (MAIA-2)

  From enrollment to 8 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: BCS+inactive

Behavioral treatment plus inhaled drug

EXPERIMENTAL

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

Combination Product: BCS+active

fMRI Control

NO INTERVENTION

Participants will undergo assessments without treatment

Interventions

BCS+inactive BEHAVIORAL

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

Behavioral treatment plus inactive drug

BCS+active COMBINATION_PRODUCT

Behavioral cough suppression therapy combined with inhaled natural substance known to desensitize sensory nerves. Treatment given twice per week for 12 sessions.

Behavioral treatment plus 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:

• To be eligible to participate, participants must meet the following criteria:
• years of age
• Diagnosis of refractory or unexplained chronic cough
• Normal chest imaging (x-ray or CT scan) within past 2 years, without change in cough symptoms
• If you a potential participant has asthma, the following criteria must be met:
• Asthma diagnosed by a pulmonary provider
• Documentation from a pulmonary provider that asthma is well-controlled
• Agree to carry prescribed rescue inhaler to each study visit
• Can tolerate, and agree to, avoid rescue inhaler use for 4 hours prior to each study visit. If rescue inhaler use is unavoidable within 4 hours of a study visit, agree to inform researchers in advance so that the session can be rescheduled.
• Normal pulmonary function testing with spirometry (FEV1/FVC of at least 70% if diagnosed with asthma) within 2 years (6 months for those with a diagnosis of asthma), without change in symptoms since (NOTE: spirometry is included as part of cough threshold testing and can serve as this criteria if the participant has not had spirometry within the designated time.)
• 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)
• Access to reliable internet, working email address (for surveys) and a smart phone (for use with CoughMonitor Watch)

You may not qualify if:

• Currently a smoker of any substance or has a positive history of smoking any substance within the last 6 months
• Currently suffering from any signs of an upper respiratory infection (other than cough)
• Hemoptysis (coughing up blood) within the last 6 months
• Pulmonary diagnosis other than asthma
• Asthma criteria - participant is deemed ineligible if screened for one or more of the following:
• Use of rescue inhaler in response to active asthma symptoms ≥ 2 times per week
• Respiratory related emergency department visit within the past 4 weeks
• Respiratory related ICU admission within the past 12 months
• Asthma exacerbation requiring systemic corticosteroid use within the past 4 weeks
• Pregnant or trying to become pregnant
• Any complaints or clinical symptoms of dysphagia
• Live with someone with chronic cough or work with someone with chronic cough who is in close proximity (e.g., within 25 feet) on a daily or nearly daily basis
• Known allergy to peppers
• Currently receiving or has received BCS therapy for management of refractory chronic cough
• Excluded concomitant medications:

Sponsors & Collaborators

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

• Amanda Gillespie, PhD

  Emory University

  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: SINGLE
• Who Masked: PARTICIPANT
• 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 (Estimated): July 29, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): March 31, 2030
• Last Updated: July 8, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

US (3)