Mechanisms of Change in Behavioral Cough Suppression Therapy for Refractory Chronic Cough
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-99
SponsorUniversity of Montana
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Asthma diagnosed by a pulmonary provider
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
BCS+inactive
BehavioralBehavioral cough suppression therapy plus inactive inhaled drug. Treatment given twice per week for 12 sessions.
BCS+active
Combination productBehavioral cough suppression therapy combined with inhaled natural substance known to desensitize sensory nerves. Treatment given twice per week for 12 sessions.
Treatment groups
135 Participants
are divided into 3 treatment groupsGroup A: Behavioral treatment plus inactive drugActive comparator 1 intervention
Group B: Behavioral treatment plus inhaled drugExperimental treatment 1 intervention
Group C: fMRI ControlNo intervention 0 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
From enrollment to 4 weeks following enrollment2
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.
Time frame
From enrollment to 4 weeks following enrollment3
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).
Time frame
From enrollment to 4 weeks following enrollment4
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)
Time frame
4 weeks following enrollment BCS+CAP and BCS+Sham participants; enrollment to 1 week post-enrollment for the fMRI control groupSecondary outcomes
1
Leicester Cough Questionnaire (LCQ)
19-item patient-report outcome measure related to the impact of cough on quality of life
Time frame
From enrollment to 19 weeks following enrollment2
Cough frequency
Ambulatory cough frequency monitoring with a specialized smartwatch, which is worn for 5 days before treatment and 5 days following treatment
Time frame
From enrollment to 11 weeks following enrollment3
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.
Time frame
From enrollment to 19 weeks following enrollment4
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.
Time frame
From enrollment to 19 weeks following enrollmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Montana
Lead sponsor
University of Colorado, Denver
Collaborator
Emory University
Collaborator
University of Melbourne
Collaborator
Source ClinicalTrials.gov