Ignite Creation Date:
2025-12-24 @ 2:32 PM
Ignite Modification Date:
2026-01-02 @ 9:36 AM
Study NCT ID:
NCT06960759
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-05-11
First Post:
2025-04-28
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Mechanisms of Change in Behavioral Cough Suppression Therapy for Refractory Chronic Cough
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000096822', 'term': 'Chronic Cough'}, {'id': 'C000726768', 'term': 'cough hypersensitivity syndrome'}], 'ancestors': [{'id': 'D003371', 'term': 'Cough'}, {'id': 'D012120', 'term': 'Respiration Disorders'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D012818', 'term': 'Signs and Symptoms, Respiratory'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 150}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-08-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-05', 'completionDateStruct': {'date': '2030-03-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-05-06', 'studyFirstSubmitDate': '2025-04-28', 'studyFirstSubmitQcDate': '2025-04-28', 'lastUpdatePostDateStruct': {'date': '2025-05-11', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-05-07', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2029-06-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Cough threshold sensory testing (CTT)', 'timeFrame': 'From enrollment to 14 weeks following enrollment', 'description': 'Measure of cough sensitivity using progressive doses of inhaled vaporized citric acid. The dose causing 5 or more coughs (C5) is the endpoint.'}, {'measure': 'Cough suppression threshold testing (CSTT)', 'timeFrame': 'From enrollment to 14 weeks following enrollment', 'description': '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.'}, {'measure': 'Urge-to-Cough Sensory Motor Threshold Difference (UTC S-M Thresh Diff)', 'timeFrame': 'From enrollment to 14 weeks following enrollment', 'description': '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).'}, {'measure': 'Blood oxygen level dependent neural responses (BOLD)', 'timeFrame': 'From enrollment to 14 weeks following enrollment', 'description': '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)'}], 'secondaryOutcomes': [{'measure': 'Leicester Cough Questionnaire (LCQ)', 'timeFrame': 'From enrollment to 23 weeks following enrollment', 'description': '19-item patient-report outcome measure related to the impact of cough on quality of life'}, {'measure': 'Cough frequency', 'timeFrame': 'From enrollment to 14 weeks following enrollment', 'description': 'Ambulatory cough frequency monitoring with a specialized smartwatch, which is worn for 5 days before treatment and 5 days following treatment'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['cough hypersensitivity syndrome', 'randomized control trial', 'neurogenic cough', 'refractory chronic cough', 'unexplained chronic cough', 'chronic cough', 'behavioral cough suppression therapy'], 'conditions': ['Chronic Cough (CC)', 'Refractory Chronic Cough', 'Unexplained Chronic Cough']}, 'referencesModule': {'references': [{'pmid': '3602068', 'type': 'BACKGROUND', 'citation': 'Losche D, Furst W, Falk M, Weickert H. [Preparation of a cytostatic-containing bone cement]. Pharmazie. 1987 Feb;42(2):97-9. German.'}, {'pmid': '38244293', 'type': 'BACKGROUND', 'citation': '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': '37118696', 'type': 'BACKGROUND', 'citation': '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': '35091204', 'type': 'BACKGROUND', 'citation': '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': '25787221', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': "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.\n\nIn this study, we will test three treatments:\n\n* BCS therapy with capsaicin (BCS+CAP),\n* BCS therapy with a placebo (BCS+Sham),\n* Capsaicin stimulation alone (CAP).\n\nThe 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.\n\nThe investigators want to find out how these treatments affect:\n\n* How sensitive someone is to things that make them cough,\n* How well they can hold back a cough when they try,\n* How their brain responds to things that cause an urge-to-cough,\n* And how much their coughing affects their quality of life.\n\nThe 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.", 'detailedDescription': '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.\n\nThis 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.\n\nThe investigators will recruit 150 participants diagnosed with RCC and randomize them into one of three treatment arms:\n\n* BCS combined with capsaicin stimulation (BCS+CAP),\n* BCS combined with sham stimulation (BCS+Sham),\n* Capsaicin stimulation alone (CAP).\n\nParticipants 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:\n\n* Cough sensory threshold (C5): the lowest concentration of citric acid causing five or more coughs,\n* 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,\n* Urge-to-cough (UTC) sensory-motor threshold difference: a measure of how perception of the need to cough relates to actual coughing behavior,\n* Blood oxygen level dependent (BOLD) neural responses using whole-brain functional MRI (fMRI) during UTC stimulation.\n\nSecondary outcomes will include patient-reported measures such as the Leicester Cough Questionnaire (LCQ) and objective ambulatory cough frequency monitoring.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '99 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Diagnosis of refractory or unexplained chronic cough\n* Normal chest x-ray within past 2 years, without change in cough symptoms\n* If diagnosed with asthma, is it well controlled\n* Normal spirometry (or FEV1/FVC of at least 70% if diagnosed with asthma) within two years, without change in symptoms since\n* Laryngoscopy or stroboscopy within 2 years without evidence of structural pathology and no change in vocal quality since exam\n* Proficient reader/speaker of English\n* Willing to take a pregnancy test before enrollment (if applicable)\n* Willing to use contraception during the study (if applicable)\n* Demonstrates understanding in study procedures and risks in order to consent\n\nExclusion Criteria:\n\n* Currently a smoker of any substance\n* Currently suffering from any signs of an upper respiratory infection (other than cough)\n* Hemoptysis (coughing up blood)\n* Pulmonary diagnosis other than asthma\n* Used an ACE-inhibitor in the past 60 days\n* Pregnant or trying to become pregnant\n* Any complaints or clinical symptoms of dysphagia\n* Live with or work with anyone with chronic cough\n\nThe following additional exclusion criteria will apply to participants at University of Colorado:\n\n* Presence of metal implants, devices or fragments in the body\n* Claustrophobia'}, 'identificationModule': {'nctId': 'NCT06960759', 'briefTitle': 'Mechanisms of Change in Behavioral Cough Suppression Therapy for Refractory Chronic Cough', 'organization': {'class': 'OTHER', 'fullName': 'University of Montana'}, 'officialTitle': 'Mechanisms of Change in Behavioral Cough Suppression Therapy for Refractory Chronic Cough', 'orgStudyIdInfo': {'id': '25-0206'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Behavioral treatment plus inactive drug', 'description': 'Participants receive behavioral cough suppression therapy (BCST) combined with an inactive inhaled substance.', 'interventionNames': ['Behavioral: Behavioral cough suppression therapy combined with inactive inhaled drug (BCS+Sham)']}, {'type': 'EXPERIMENTAL', 'label': 'Behavioral treatment plus inhaled drug', 'description': 'Participants receive behavioral cough suppression therapy (BCST) combined with inhaled vaporized drug designed to enhance BCST', 'interventionNames': ['Combination Product: Behavioral cough suppression therapy combined with capsaicin inhalation (BCS+CAP)']}, {'type': 'EXPERIMENTAL', 'label': 'Inhaled drug', 'description': 'Participants inhale a drug designed to desensitize the cough reflex.', 'interventionNames': ['Drug: Inhaled capsaicin (CAP)']}], 'interventions': [{'name': 'Behavioral cough suppression therapy combined with inactive inhaled drug (BCS+Sham)', 'type': 'BEHAVIORAL', 'description': 'Behavioral cough suppression therapy plus inactive inhaled drug. Treatment given twice per week for 12 sessions.', 'armGroupLabels': ['Behavioral treatment plus inactive drug']}, {'name': 'Behavioral cough suppression therapy combined with capsaicin inhalation (BCS+CAP)', 'type': 'COMBINATION_PRODUCT', 'description': 'Behavioral cough suppression therapy combined with inhaled capsaicin (cough stimulant). Treatment given twice per week for 12 sessions.', 'armGroupLabels': ['Behavioral treatment plus inhaled drug']}, {'name': 'Inhaled capsaicin (CAP)', 'type': 'DRUG', 'description': 'Repeated inhalation of diluted capsaicin in increasing concentrations. Treatment given twice per week for 12 sessions.', 'armGroupLabels': ['Inhaled drug']}]}, 'contactsLocationsModule': {'locations': [{'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'contacts': [{'name': 'Marie Jetté, PhD', 'role': 'CONTACT', 'email': 'marie.jette@cuanschutz.edu', 'phone': '303-724-3918'}], 'facility': 'University of Colorado Anschutz Medical Campus', 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}, {'zip': '30322', 'city': 'Atlanta', 'state': 'Georgia', 'country': 'United States', 'contacts': [{'name': 'Amanda Gillespie, PhD', 'role': 'CONTACT', 'email': 'amanda.i.gillespie@emory.edu', 'phone': '404-778-3381'}], 'facility': 'Emory University', 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}, {'zip': '59812', 'city': 'Missoula', 'state': 'Montana', 'country': 'United States', 'contacts': [{'name': 'Laurie J Slovarp, PhD', 'role': 'CONTACT', 'email': 'laurie.slovarp@umontana.edu', 'phone': '406-243-2107'}], 'facility': 'University of Montana', 'geoPoint': {'lat': 46.87215, 'lon': -113.994}}], 'centralContacts': [{'name': 'Laurie J Slovarp, PhD', 'role': 'CONTACT', 'email': 'laurie.slovarp@umontana.edu', 'phone': '406-243-2107'}, {'name': 'Marie Jetté, PhD', 'role': 'CONTACT', 'email': 'marie.jette@cuanschutz.edu'}], 'overallOfficials': [{'name': 'Laurie J Slovarp, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Montana'}, {'name': 'Marie Jetté, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Colorado, Denver'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Montana', 'class': 'OTHER'}, 'collaborators': [{'name': 'University of Colorado, Denver', 'class': 'OTHER'}, {'name': 'Emory University', 'class': 'OTHER'}, {'name': 'University of Melbourne', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Laurie Slovarp', 'investigatorAffiliation': 'University of Montana'}}}}