Chronic Cough (CC)Phase 2CoughLESSNCT06960759
Mechanisms of Change in Behavioral Cough Suppression Therapy for Refractory Chronic Cough
A Phase 2 study testing BCS+inactive and BCS+active in people with Chronic Cough (CC) and Refractory Chronic Cough, run by University of Montana at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Chronic Cough (CC), Refractory Chronic Cough, Unexplained Chronic Cough
- What is being tested?
- BCS+inactive and BCS+active
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 135 participants
- Where
- 3 sitesUnited States
- Study dates
- 13 Aug 2026to 31 Mar 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be eligible to participate, participants must meet the following criteria:
- 18 - 99 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
Show all 17Show fewer
- 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)
- Demonstrates understanding in study procedures and risks in order to consent
- Available, and willing, to comply to all study procedures and clinic visits.
Who cannot join
- Any of the following will be grounds for exclusion from the study:
- 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:
Show all 25Show fewer
- 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:
- Inhaled pulmonary medications (inhaled corticosteroids, short-acting beta agonists, long-acting beta-agonist, short-acting muscarinic antagonists), unless prescribed for asthma by pulmonary provider: 30 days prior to Visit 1 through completion of study participation
- ACE inhibitor (benazepril, captopril, enalapril, fosiniopril, lisinopril, perindopril, quinapril, ramipril, trandolapril): 30 days prior to Visit 1 through completion of study participation.
- Narcotic antitussive (hydrocodone, oxycodone, morphine, codeine, tramadol): 7 days prior to Visit 1 through completion of study participation
- Non-narcotic antitussive (benzonatate/Tessalon, dextromethorphan/Delsym, carbetapentane/Solotuss): 7 days prior to Visit 1 through completion of study
- P2X3 receptor antagonist (gefapixant/Lyfnua): 14 days prior to Visit 1 through completion of study
- Any off-label prescription medication prescribed for cough (pregabalin/Lyrica, gabapentin/Neurontin, amitriptyline/Elavil): 14 days prior to Visit 1 through completion of study *if a neuromodulator is prescribed for something other than cough, participant must be on a stable dose for a minimum of 7 days
- The following additional exclusion criteria will apply to participants who will undergo fMRI:
- Presence of metal implants, devices or fragments (e.g., shrapnel) in the body
- Claustrophobia
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Marie Jetté, PhD contact
United States3 sites, 3 recruiting
- Recruiting
Emory University
Atlanta, Georgia, 30322
Amanda Gillespie, PhD, 404-778-3381, amanda.i.gillespie@emory.edu
- Not yet recruiting
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
Marie Jetté, PhD, 303-724-3918, marie.jette@cuanschutz.edu
- Recruiting
University of Montana
Missoula, Montana, 59812
Laurie J Slovarp, PhD, 406-243-2107, laurie.slovarp@umontana.edu
About this study
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.
Read more
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.
Read the detailed description
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 an inhaled substance designed to enhance the effect of BCS treatment. The active inhaled substance used in the study 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. Inhalation of this substance has been shown to be safe across multiple studies.
The investigators will recruit 135 participants diagnosed with RCC. 100 participants will be randomized into one of two treatment arms -- BCS combined with an active inhaled substance, and BCS combined with an inactive inhalant. A non-randomized no-treatment control group (n=35) will be included to provide a control comparison to fMRI.
Participants in the treatment arms 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 (CS Thresh Diff): the ability to suppress cough when instructed, quantified by 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 (UTC S-M Thresh Diff): 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.
The following patient-report outcome measures (PROMS) will be included as secondary outcomes:
- Leicester Cough Questionnaire (LCQ): Assesses patient-reported cough-related quality of life, relevant for assessing the broader impact of treatment.
- PROMIS-Global Health: Assesses patient-reported generalized quality of life, relevant for assessing the broader impact of treatment.
- Voice Handicap Index-10 (VHI-10): Assesses patient-reported impact of voice problems and is relevant for assessing the broader impact of treatment.
- Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ): Assesses patient-reported laryngeal sensory symptoms and is relevant for assessing the broader impact of treatment
- Multidimensional Assessment of Interoceptive Awareness (MAIA-2): Assesses patient-reported awareness and regulation of bodily sensations and is relevant for assessing the broader impact of treatment
- Patient Global Impression of Severity (PGI-S): Assesses patient-reported overall perception of cough severity and is relevant for assessing the broader impact of treatment
- Patient Global of Impression of Change (PGI-C): Assesses patient-reported impression of change related to treatment and is relevant for assessing the broader impact of treatment
- PROMIS-Sleep: Assesses patient-reported sleep quality and is relevant for assessing the broader impact of treatment
Ambulatory cough frequency monitoring will also be included as a secondary outcome. This data will be collected with the CoughMonitor smartwatch by Hyfe, Inc.
The investigators hypothesize that both treatments will lead to desensitization of cough sensitivity (i.e., increase in C5). We further hypothesize that the combination of BCS+active inhaled treatment will provide the greatest therapeutic benefit on all outcome measures due to simultaneous peripheral desensitization and central sensory-motor modulation. Regarding fMRI, we hypothesize that both treatments will result in increased activity in areas responsible for motor inhibition (e.g., prefrontal cortex).
- Being tested
- BCS+inactive, BCS+active
- Keywords
- cough hypersensitivity syndrome, randomized control trial, neurogenic cough, refractory chronic cough, unexplained chronic cough, chronic cough, behavioral cough suppression therapy
- Medical subject headings
- Chronic Cough, cough hypersensitivity syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCS+inactiveBehavioural
Behavioral cough suppression therapy plus inactive inhaled drug. Treatment given twice per week for 12 sessions.
BCS+activeCombination product
Behavioral cough suppression therapy combined with inhaled natural substance known to desensitize sensory nerves. Treatment given twice per week for 12 sessions.
| Study group | Role | What they receive |
|---|---|---|
| Behavioral treatment plus inactive drug | Active comparator | Participants receive behavioral cough suppression therapy (BCST) combined with an inactive inhaled substance. Receives: 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 Receives: Combination Product: BCS+active |
| fMRI Control | No intervention | Participants will undergo assessments without treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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).
Measured: 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)
Measured: 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)
19-item patient-report outcome measure related to the impact of cough on quality of life
Measured: From enrollment to 19 weeks following enrollment
Cough frequency
Ambulatory cough frequency monitoring with a specialized smartwatch, which is worn for 5 days before treatment and 5 days following treatment
Measured: From enrollment to 11 weeks following enrollment
Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ)
The NLHQ consists of 14 questions assessing laryngeal paresthesia (i.e., abnormal sensory symptoms) commonly seen in RCC. A lower score indicates greater paresthesia.
Measured: From enrollment to 19 weeks following enrollment
Voice Handicap Index - 10 (VHI-10)
The VHI-10 assesses the functional impact of dysphonia on life, which is often seen in patients with RCC. The higher the score, the greater the impact of dysphonia on life.
Measured: From enrollment to 19 weeks following enrollment
Multidimensional Assessment of Interoceptive Awareness (MAIA-2)
The MAIA-2 has 14 questions and is collected via an electronic survey at the Baseline Visit (Visit 1) and Visit 14 (PT1). The primary purpose of MAIA-2 is to assess participants general interoceptive awareness (i.e., awareness of internal bodily sensations). The key domains are noticing, not-distracting, emotional awareness, self-regulation, body listening, and trusting.
Measured: From enrollment to 8 weeks following enrollment
PROMIS - Global Health
The PROMIS - Global Health assesses general, health-related quality of life. This instrument has 10 questions in the key domains of physical health, mental health, social health, pain, and fatigue.
Measured: From enrollment to 11 weeks following enrollment
PROMIS - Sleep
The PROMIS - Sleep questionnaire assesses quality of life relating to sleep. It has 10 questions.
Measured: From enrollment to 8 weeks following enrollment
Patient Global Impression of Severity (PGI-S)
PGI-S is a single, global severity construct that assesses participants overall perception of cough severity. Using the single question of "How would you rate the overall severity of your cough?", participants will rate their perception of cough severity between 0-4 (0 representing "no cough" and 4 representing "very severe".
Measured: From enrollment to 19 weeks following enrollment
Patient Global Impression of Change (PGI-C)
PGI-C is a single, global change construct used to assess participants overall perception of change following a treatment. It will be asked specifically in regard to treatment for chronic cough using the single question of "Since beginning treatment, how would you describe the overall change in your chronic cough?". Participants will rate their perception of change between 1-7 (1 representing "very much improved", 4 representing "no change", and 7 representing "very much worse".
Measured: From enrollment to 19 weeks following enrollment
Study Specific Questions (3; 3-SSQ)
There are three, study specific questions that will be collected as a PROM at Baseline Visit (Visit 1), Visit 8, Visit 14/PT1, PT2, and PT3 to assess frequency of daily uncontrollable coughing, frequency of daily urinary incontinence, and frequency of daily urge-to-cough.
Measured: From enrollment to 19 weeks following enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2025
- Study start13 Aug 2026
- Primary completion30 Jun 2029 (estimated)
- Study completion31 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Chronic Cough (CC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 135 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Montana
- Sponsor type
- University, hospital or other
- Collaborators
- University of Colorado, Denver, Emory University, University of Melbourne
- Responsible party
- Principal investigator, Laurie Slovarp, University of Montana
- Investigators
- Laurie J Slovarp, PhD, Principal investigator, University of MontanaMarie Jetté, PhD, Principal investigator, University of Colorado, DenverAmanda Gillespie, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06960759
- Sponsor's protocol ID
- 25-0206
- Acronym
- CoughLESS
- Status last verified
- Aug 2026
- First submitted
- 28 Apr 2025
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Losche D, Furst W, Falk M, Weickert H. [Preparation of a cytostatic-containing bone cement]. Pharmazie. 1987 Feb;42(2):97-9. German.
PubMed 3602068Moe 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.
PubMed 38244293Slovarp 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.
PubMed 37118696Slovarp 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.
PubMed 35091204Chamberlain 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.
PubMed 25787221
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Change in Behavioral Cough Suppression Therapy for Refractory Chronic Cough
- ClinicalTrials.gov ID
- NCT06960759
- Acronym / sponsor ID
- CoughLESS / 25-0206
- Keywords
- cough hypersensitivity syndrome, randomized control trial, neurogenic cough, refractory chronic cough, unexplained chronic cough, chronic cough, behavioral cough suppression therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 135 participants (estimated)
- Lead sponsor
- University of MontanaUniversity, hospital or other
- Collaborators
- University of Colorado, Denver, Emory University, University of Melbourne
- Study start
- 13 Aug 2026 (actual)
- Primary completion
- 30 Jun 2029 (estimated)
- Study completion
- 31 Mar 2030 (estimated)
- First posted
- 7 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 an inhaled substance designed to enhance the effect of BCS treatment. The active inhaled substance used in the study 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. Inhalation of this substance has been shown to be safe across multiple studies.
The investigators will recruit 135 participants diagnosed with RCC. 100 participants will be randomized into one of two treatment arms -- BCS combined with an active inhaled substance, and BCS combined with an inactive inhalant. A non-randomized no-treatment control group (n=35) will be included to provide a control comparison to fMRI.
Participants in the treatment arms 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 (CS Thresh Diff): the ability to suppress cough when instructed, quantified by 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 (UTC S-M Thresh Diff): 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.
The following patient-report outcome measures (PROMS) will be included as secondary outcomes:
- Leicester Cough Questionnaire (LCQ): Assesses patient-reported cough-related quality of life, relevant for assessing the broader impact of treatment.
- PROMIS-Global Health: Assesses patient-reported generalized quality of life, relevant for assessing the broader impact of treatment.
- Voice Handicap Index-10 (VHI-10): Assesses patient-reported impact of voice problems and is relevant for assessing the broader impact of treatment.
- Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ): Assesses patient-reported laryngeal sensory symptoms and is relevant for assessing the broader impact of treatment
- Multidimensional Assessment of Interoceptive Awareness (MAIA-2): Assesses patient-reported awareness and regulation of bodily sensations and is relevant for assessing the broader impact of treatment
- Patient Global Impression of Severity (PGI-S): Assesses patient-reported overall perception of cough severity and is relevant for assessing the broader impact of treatment
- Patient Global of Impression of Change (PGI-C): Assesses patient-reported impression of change related to treatment and is relevant for assessing the broader impact of treatment
- PROMIS-Sleep: Assesses patient-reported sleep quality and is relevant for assessing the broader impact of treatment
Ambulatory cough frequency monitoring will also be included as a secondary outcome. This data will be collected with the CoughMonitor smartwatch by Hyfe, Inc.
The investigators hypothesize that both treatments will lead to desensitization of cough sensitivity (i.e., increase in C5). We further hypothesize that the combination of BCS+active inhaled treatment will provide the greatest therapeutic benefit on all outcome measures due to simultaneous peripheral desensitization and central sensory-motor modulation. Regarding fMRI, we hypothesize that both treatments will result in increased activity in areas responsible for motor inhibition (e.g., prefrontal cortex).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Behavioral treatment plus inactive drug | Active comparator | Behavioral: BCS+inactiveParticipants receive behavioral cough suppression therapy (BCST) combined with an inactive inhaled substance. |
| Behavioral treatment plus inhaled drug | Experimental | Combination Product: BCS+activeParticipants receive behavioral cough suppression (BCS) therapy combined with inhaled drug designed to enhance BCS therapy |
| fMRI Control | No intervention | –Participants will undergo assessments without treatment |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 18 - 99 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:
- 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.)
Key exclusion criteria (25 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BCS+inactiveBehavioral cough suppression therapy plus inactive inhaled drug. Treatment given twice per week for 12 sessions. | Behavioural | Behavioral treatment plus inactive drug |
| BCS+activeBehavioral cough suppression therapy combined with inhaled natural substance known to desensitize sensory nerves. Treatment given twice per week for 12 sessions. | Combination product | Behavioral treatment plus inhaled drug |
Primary outcome
Cough threshold sensory testing (CTT)
Time frame: From enrollment to 4 weeks following enrollment
Measure of cough sensitivity using progressive doses of inhaled vaporized citric acid. The dose causing 5 or more coughs (C5) is the endpoint.
Cough suppression threshold difference (CS Thresh Diff)
Time frame: From enrollment to 4 weeks following enrollment
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.
Urge-to-Cough Sensory Motor Threshold Difference (UTC S-M Thresh Diff)
Time frame: From enrollment to 4 weeks following enrollment
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).
Blood oxygen level dependent neural responses (BOLD)
Time frame: 4 weeks following enrollment BCS+CAP and BCS+Sham participants; enrollment to 1 week post-enrollment for the fMRI control group
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)
10 secondary outcomes
Leicester Cough Questionnaire (LCQ)
Time frame: From enrollment to 19 weeks following enrollment
Cough frequency
Time frame: From enrollment to 11 weeks following enrollment
Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ)
Time frame: From enrollment to 19 weeks following enrollment
Voice Handicap Index - 10 (VHI-10)
Time frame: From enrollment to 19 weeks following enrollment
Multidimensional Assessment of Interoceptive Awareness (MAIA-2)
Time frame: From enrollment to 8 weeks following enrollment
PROMIS - Global Health
Time frame: From enrollment to 11 weeks following enrollment
PROMIS - Sleep
Time frame: From enrollment to 8 weeks following enrollment
Patient Global Impression of Severity (PGI-S)
Time frame: From enrollment to 19 weeks following enrollment
Patient Global Impression of Change (PGI-C)
Time frame: From enrollment to 19 weeks following enrollment
Study Specific Questions (3; 3-SSQ)
Time frame: From enrollment to 19 weeks following enrollment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- Background: PubMed 3602068Losche D, Furst W, Falk M, Weickert H. [Preparation of a cytostatic-containing bone cement]. Pharmazie. 1987 Feb;42(2):97-9. German.
- Background: PubMed 38244293Moe 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.
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- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marie Jetté, PhD contact
Laurie J Slovarp, PhD principal investigator
University of Montana
Marie Jetté, PhD principal investigator
University of Colorado, Denver
Amanda Gillespie, PhD principal investigator
Emory University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BCS+inactive and BCS+active in people with Chronic Cough (CC) and Refractory Chronic Cough, run by University of Montana at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Laurie J Slovarp, PhD (406-243-2107, laurie.slovarp@umontana.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cough threshold sensory testing (CTT) (time frame: From enrollment to 4 weeks following enrollment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06960759, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026.