Chronic Disease, Cough
Conditions
Keywords
refractory chronic cough, behavioral cough suppression therapy
Brief summary
The goal of this randomized, placebo-controlled, clinical trial is to develop and test the efficacy of an Internet-based behavioral intervention for refractory chronic cough. The main questions it aims to answer are: * What are the best recruitment pathways to find people living with refractory chronic cough in Montana? * Is Internet-Behavioral Cough Suppression Therapy (iBCST) efficacious? * Do iBCST participants find it satisfactory? * Is using Hyfe research app to monitor cough frequency feasible in rural areas? Participants will complete iBCST or a placebo treatment virtually. Some participants will take part in qualitative interviews and use Hyfe research app for ambulatory cough frequency monitoring.
Interventions
BEHAVIORALInternet-Behavioral Cough Suppression Therapy
Participants will access training modules to learn behavioral techniques and will implement them in daily life over a four-week period.
BEHAVIORALSham Treatment
Participants will access training modules to learn behavioral techniques and will implement them in daily life over a four-week period.
Sponsors
University of Montana
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* No barriers to using a computer or smartphone (e.g., no significant fine motor or visual problems). * Internet and e-mail access and the ability to use it. * Suffering from a cough lasting at least eight weeks that is: * Largely unproductive (cough up no more than a few teaspoons worth of clear or white sputum or mucus in a 24-hour period). * Report of cough triggered by identifiable stimuli including and not limited to any combination of the following: cold air, talking, laughing, taking a deep breath, exercise, crumbly foods, strong smells or odors, fumes from paint or cleaning sprays. * Often preceded by the sensation of an urge-to-cough (e.g., tickle or itch) at the level of the throat. * Self-report of receiving the following assessments for current cough symptoms with unremarkable results: * Physical evaluation by at least one physician. * Chest x-ray. * Willingness to avoid other potential cough treatments during the course of the study (or alert study personnel if alternative treatment is implemented out of necessity).
Exclusion criteria
* Current smoker of any substance. * Diagnosis of any of the following: * Respiratory disease (e.g., chronic obstructive pulmonary disease, asthma) * Neurogenic disease (e.g., Parkinson's disease, cerebrovascular disease) * Head and neck cancer * Self-report of difficulty swallowing since having chronic cough * Use of the following medication: * Angiotensin-converting enzyme inhibitor (ACE-I) in the past four weeks: benzapril (Lotensin), Captopril (Capoten), Enalapril/Enalaprilat (Vasotec oral and injectable), Fosinopril (Monopril), Lisinopril (Zestril and Prinivil), Moexipril (Univasc), Perindopril (Aceon), Quinapril (Accupril), Ramipril (Altace), and Trandolapril (Mavik). * Use of a neuromodulator medication in the past 48 hours: Neurontin (Gabapentin) and amitriptyline. * Individuals with dysphonia (abnormal voice; either self-reported or perceived by study personnel during enrollment interview) will be excluded unless they have had a normal laryngoscopy (endoscopic assessment of the larynx) by an otolaryngologist (ENT) within the past year specifically for their cough.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Leicester Cough Questionnaire | Pre-treatment, one-week post-treatment, one-month post-treatment | Cough-related quality of life will be measured with the Leicester Cough Questionnaire (LCQ), a valid, reliable, and repeatable measure of cough-related quality of life. The LCQ is a 19-item questionnaire containing physical, psychological, and social domains. Scores for the LCQ include mean scores for each domain (ranging from 1 to 7) and a total score calculated as the sum of the domain scores (ranging from 3 to 21). A higher score indicates better quality of life. A change in 1.3 is considered clinically significant. The LCQ total score was the primary outcome measure in this study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cough Severity Visual Analog Scale | Pre-intervention, one-week post-treatment, one-month post-treatment | Cough Severity Visual Analog Scale (VAS) is a 100-millimeter line with anchors of 0 no problem and 100 worst possible problem where participants place a mark to represent the severity of their current cough problem. A reduction of at least 30-millimeters is considered clinically meaningful for the Cough Severity VAS. |
Countries
United States
Participant flow
Recruitment details
Individuals with refractory chronic cough in the United States were recruited for the study via social media campaigns, newspaper advertisements, flyers sent to voice and upper airway clinics, word-of-mouth, and Facebook support groups. Recruitment took place from May 2023-2024.
Participants by arm
| Arm | Count |
|---|---|
| Internet-Behavioral Cough Suppression Therapy Participants will watch treatment-specific educational and training videos and perform the training exercises as recommended. There are a total of five videos ranging from 2-5 minutes in length. Participants will be asked to watch the videos at least once weekly. Daily training exercises will be discussed in the videos and should take no more than a few minutes to complete every day. All exercises are non-invasive and are not physically demanding. Each week participants will complete a progress check question that will take less than one minute to answer, indicating whether they are watching the videos and completing the exercises as recommended. | 23 |
| Sham Treatment Participants will watch sham treatment-specific educational and training videos and perform the training exercises as recommended. There are a total of five videos ranging from 2-5 minutes in length. Participants will be asked to watch the videos at least once weekly. Daily training exercises will be discussed in the videos and should take no more than a few minutes to complete every day. All exercises are non-invasive and are not physically demanding. Each week participants will complete a progress check question that will take less than one minute to answer, indicating whether they are watching the videos and completing the exercises as recommended. | 16 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 4 |
Baseline characteristics
| Characteristic | Sham Treatment | Total | Internet-Behavioral Cough Suppression Therapy |
|---|---|---|---|
| Age, Continuous | 59.3 Age STANDARD_DEVIATION 8.5 | 60.5 Age STANDARD_DEVIATION 9 | 61.2 Age STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 39 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 37 Participants | 23 Participants |
| Sex: Female, Male Female | 13 Participants | 34 Participants | 21 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 16 |
| other Total, other adverse events | 0 / 23 | 0 / 16 |
| serious Total, serious adverse events | 0 / 23 | 0 / 16 |
Outcome results
Primary
Leicester Cough Questionnaire
Cough-related quality of life will be measured with the Leicester Cough Questionnaire (LCQ), a valid, reliable, and repeatable measure of cough-related quality of life. The LCQ is a 19-item questionnaire containing physical, psychological, and social domains. Scores for the LCQ include mean scores for each domain (ranging from 1 to 7) and a total score calculated as the sum of the domain scores (ranging from 3 to 21). A higher score indicates better quality of life. A change in 1.3 is considered clinically significant. The LCQ total score was the primary outcome measure in this study.
Time frame: Pre-treatment, one-week post-treatment, one-month post-treatment
Population: One participant in the IBCST group was lost to follow up at one-month post-treatment and values are missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Internet-Behavioral Cough Suppression Therapy | Leicester Cough Questionnaire | Pre-intervention | 9.04 Total LCQ Score | Standard Deviation 7.32 |
| Internet-Behavioral Cough Suppression Therapy | Leicester Cough Questionnaire | One-week post-treatment | 12.78 Total LCQ Score | Standard Deviation 12.89 |
| Internet-Behavioral Cough Suppression Therapy | Leicester Cough Questionnaire | one-month post-treatment | 13.04 Total LCQ Score | Standard Deviation 4.31 |
| Sham Treatment | Leicester Cough Questionnaire | Pre-intervention | 8.86 Total LCQ Score | Standard Deviation 7.6 |
| Sham Treatment | Leicester Cough Questionnaire | One-week post-treatment | 9.44 Total LCQ Score | Standard Deviation 12.27 |
| Sham Treatment | Leicester Cough Questionnaire | one-month post-treatment | 9.70 Total LCQ Score | Standard Deviation 18.38 |
Comparison: The null hypothesis was there would be no significant difference in LCQ total score change from baseline to one-week post-treatment between groups.p-value: 0.01495% CI: [0.72, 5.76]ANCOVA
Secondary
Cough Severity Visual Analog Scale
Cough Severity Visual Analog Scale (VAS) is a 100-millimeter line with anchors of 0 no problem and 100 worst possible problem where participants place a mark to represent the severity of their current cough problem. A reduction of at least 30-millimeters is considered clinically meaningful for the Cough Severity VAS.
Time frame: Pre-intervention, one-week post-treatment, one-month post-treatment
Population: One participant in the IBCST group was lost to follow up at one-month post-treatment and values are missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Internet-Behavioral Cough Suppression Therapy | Cough Severity Visual Analog Scale | Pre-intervention | 49 VAS Total Score | Standard Deviation 15.97 |
| Internet-Behavioral Cough Suppression Therapy | Cough Severity Visual Analog Scale | One-week post-treatment | 33.94 VAS Total Score | Standard Deviation 21.32 |
| Internet-Behavioral Cough Suppression Therapy | Cough Severity Visual Analog Scale | One-month post-treatment | 44.18 VAS Total Score | Standard Deviation 22.85 |
| Sham Treatment | Cough Severity Visual Analog Scale | Pre-intervention | 49.08 VAS Total Score | Standard Deviation 22.39 |
| Sham Treatment | Cough Severity Visual Analog Scale | One-week post-treatment | 50.08 VAS Total Score | Standard Deviation 22.39 |
| Sham Treatment | Cough Severity Visual Analog Scale | One-month post-treatment | 56.42 VAS Total Score | Standard Deviation 23.74 |
Comparison: The null hypothesis was there would be no significant difference in Cough Severity VAS Scores from baseline to one-week post-treatment between groups.p-value: 0.05695% CI: [-32.7, 0.46]ANCOVA