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The purpose of this study is to investigate a modified behavioral treatment for chronic cough due to cough hypersensitivity syndrome (CHS). This type of CC is a non-productive cough that is due, in part, to over-expression of transient receptor potential vanilliod (TRPV) receptors in the airway epithelium, which contribute to a dry cough elicited by typically non-tussive stimuli (e.g., cold air, smells) or by low doses of tussive stimuli (e.g., smoke). Currently available treatment options are limited to neuromodulator medications (e.g., gabapentin, amytriptiline) and behavioral cough suppression therapy (BCST), neither of which is 100% effective. The primary component of BCST is teaching patients to suppress their cough in the presence of an urge-to-cough. Studies have confirmed a reduction in cough sensitivity (as tested with inhaled capsaicin) following 1-4 weeks of successful cough suppression. However, patients with severe CHS are not able to suppress their cough in the presence of uncontrollable environmental stimuli and, hence, do not respond well to the therapy. The purpose of this study is to determine the potential of treating CHS by implementing BCST while stimulating cough with progressive concentrations of inhaled diluted aerosolized capsaicin. The investigators hypothesize this treatment will result in a reduction in cough-reflex sensitivity, cough-related quality of life, and cough frequency.
The study will be a randomized, placebo-controlled, blinded study. It will take place in three phases, across 7 weeks.
WEEK 1: BASELINE TESTING AND TRAINING (approximate time = 1 hour).
(Following baseline testing, participants will be randomly assigned to either the treatment group or placebo group.)
WEEKS 2-4: TREATMENT. Participants will attend treatment sessions twice per week for three weeks. Participants will use the breathing strategies following inhalation of either progressive doses of diluted capsaicin (experimental condition) or repeated exposures to a single sub-threshold concentration of diluted capsaicin (placebo condition). Participants will do this no more than twelve times per session. Each session will take approximately 45 minutes. If a participant misses a treatment session, the investigators will attempt to re-schedule that session. Each participant must complete at least five of treatment sessions to remain in the study.
WEEKS 5 AND 7: POST-TREATMENT TESTING. Outcome measures, as in the baseline phase, will be take at one-week and three-weeks post-treatment. The LCQ will be measured again at three-months post-treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Supra-threshold capsaicin | Experimental | Participants will be exposed to progressively increasing concentrations of aerosolized capsaicin (the ingredient in chili peppers that makes them spicy, and a known cough stimulant) to stimulate an urge-to-cough. Participants will be coached to implement cough suppression strategies following each exposure. |
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| Sub-threshold capsaicin | Placebo Comparator | Participants will be exposed repeatedly to a single sub-threshold dose of aerosolized capsaicin through a nebulizer during treatment. This sub-threshold dose will elicit minimal or no urge-to-cough. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Supra-threshold and progressive doses of diluted capsaicin via a Koko Digidoser nebulizer | Biological | Participants will be exposured to increasing doses of aerosolized capsaicin (a known cough stimulant) through the Koko Digidoser nebulizer, while implementing behavioral cough suppression strategies. The concentration of capsaicin will increase incrementally as tolerated, as long as participants are still able to suppress cough. The concentration will never exceed 1000 micromolar. Participants will attend 6 treatment sessions and be given up to 12 exposures per treatment session. Participants will be encouraged to use cough suppression strategies outside of treatment sessions as much as possible to attempt to suppress cough. |
| Measure | Description | Time Frame |
|---|---|---|
| Leicester Cough Questionnaire (LCQ) | The Leicester Cough Questionnaire (LCQ) is a 19-item validated patient-report questionnaire that measures the impact of cough on quality of life. It takes about 5 minutes to complete and results in three domain scores (Social, Psychological, and Physical), and one Total score. Domain scores are averages of the questions that make up each domain. Minimum and maximum domain scores are 1 and 7, respectively. The domain scores are summed to determine the Total score, which can range from 3 to 21. A higher score means less impact on quality of life. The change in LCQ was determined by subtracting the Total LCQ score at baseline from the Total LCQ score at 3 weeks post-treatment. A positive LCQ change score indicates an improvement. | The LCQ will be measured before treatment and three weeks following treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Urge-to-Cough Testing | Urge-to-cough (UTC) testing involves presenting participants to various scents and vocal and breathing tasks (12 tasks in total) and asking them to rate their maximum perceived UTC on a scale from 0 (no UTC) to 10 (maximum UTC). The UTC score for each testing session is the sum of the the UTC scores from each individual task. This results in a possible score range from 0 (no UTC on any tasks) to 120 (score of 10 on every UTC task). UTC change is determined by subtracting the UTC score on each task at baseline from the UTC score for each task at 3 weeks post-treatment and then summing those scores. A negative UTC change score indicates the UTC score was lower post-treatment relative to baseline, which indicates an improvement. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Laurie J Slovarp, PhD | University of Montana | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Montana | Missoula | Montana | 59812 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35091204 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Supra-threshold Capsaicin | Participants will be exposed to progressively increasing concentrations of aerosolized capsaicin (the ingredient in chili peppers that makes them spicy, and a known cough stimulant) to stimulate an urge-to-cough. Participants will be coached to implement cough suppression strategies following each exposure. Supra-threshold and progressive doses of diluted capsaicin via a Koko Digidoser nebulizer: Participants will be exposured to increasing doses of aerosolized capsaicin (a known cough stimulant) through the Koko Digidoser nebulizer, while implementing behavioral cough suppression strategies. The concentration of capsaicin will increase incrementally as tolerated, as long as participants are still able to suppress cough. The concentration will never exceed 1000 micromolar. Participants will attend 6 treatment sessions and be given up to 12 exposures per treatment session. Participants will be encouraged to use cough suppression strategies outside of treatment sessions as much as possible to attempt to suppress cough. |
| FG001 | Sub-threshold Capsaicin | Participants will be exposed repeatedly to a single sub-threshold dose of aerosolized capsaicin through a nebulizer during treatment. This sub-threshold dose will elicit minimal or no urge-to-cough. Sub-threshold doses of diluted capsiacin via a KoKo Digidoser nebulizer: Participants will be repeatedly exposed to a sub-threshold dose of aerosolized capsaicin through the KoKo Digidoser nebulizer during treatment sessions. Participants will attend 6 treatment sessions and be given up to 12 exposures per treatment session. Participants will be encouraged to use cough suppression strategies outside of treatment sessions as much as possible to attempt to suppress cough. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Supra-threshold Capsaicin | Participants will be exposed to progressively increasing concentrations of aerosolized capsaicin (the ingredient in chili peppers that makes them spicy, and a known cough stimulant) to stimulate an urge-to-cough. Participants will be coached to implement cough suppression strategies following each exposure. Supra-threshold and progressive doses of diluted capsaicin via a Koko Digidoser nebulizer: Participants will be exposured to increasing doses of aerosolized capsaicin (a known cough stimulant) through the Koko Digidoser nebulizer, while implementing behavioral cough suppression strategies. The concentration of capsaicin will increase incrementally as tolerated, as long as participants are still able to suppress cough. The concentration will never exceed 1000 micromolar. Participants will attend 6 treatment sessions and be given up to 12 exposures per treatment session. Participants will be encouraged to use cough suppression strategies outside of treatment sessions as much as possible to attempt to suppress cough. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Leicester Cough Questionnaire (LCQ) | The Leicester Cough Questionnaire (LCQ) is a 19-item validated patient-report questionnaire that measures the impact of cough on quality of life. It takes about 5 minutes to complete and results in three domain scores (Social, Psychological, and Physical), and one Total score. Domain scores are averages of the questions that make up each domain. Minimum and maximum domain scores are 1 and 7, respectively. The domain scores are summed to determine the Total score, which can range from 3 to 21. A higher score means less impact on quality of life. The change in LCQ was determined by subtracting the Total LCQ score at baseline from the Total LCQ score at 3 weeks post-treatment. A positive LCQ change score indicates an improvement. | Posted | Mean | Standard Deviation | score on a scale | The LCQ will be measured before treatment and three weeks following treatment |
|
Adverse events were collected during the treatment period and for three weeks following the treatment period for a total of 9 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Supra-threshold Capsaicin | Participants will be exposed to progressively increasing concentrations of aerosolized capsaicin (the ingredient in chili peppers that makes them spicy, and a known cough stimulant) to stimulate an urge-to-cough. Participants will be coached to implement cough suppression strategies following each exposure. Supra-threshold and progressive doses of diluted capsaicin via a Koko Digidoser nebulizer: Participants will be exposured to increasing doses of aerosolized capsaicin (a known cough stimulant) through the Koko Digidoser nebulizer, while implementing behavioral cough suppression strategies. The concentration of capsaicin will increase incrementally as tolerated, as long as participants are still able to suppress cough. The concentration will never exceed 1000 micromolar. Participants will attend 6 treatment sessions and be given up to 12 exposures per treatment session. Participants will be encouraged to use cough suppression strategies outside of treatment sessions as much as possible to attempt to suppress cough. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Laurie Slovarp | University of Montana | 406-243-2107 | laurie.slovarp@umontana.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 22, 2022 | Aug 30, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003371 | Cough |
| D000096822 | Chronic Cough |
| C000726768 | cough hypersensitivity syndrome |
| ID | Term |
|---|---|
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
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One group will receive the placebo treatment while the second group receives the active treatment.
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Participants and outcome assessors will be blinded to group assignment (active treatment vs placebo).
|
| Sub-threshold doses of diluted capsiacin via a KoKo Digidoser nebulizer | Biological | Participants will be repeatedly exposed to a sub-threshold dose of aerosolized capsaicin through the KoKo Digidoser nebulizer during treatment sessions. Participants will attend 6 treatment sessions and be given up to 12 exposures per treatment session. Participants will be encouraged to use cough suppression strategies outside of treatment sessions as much as possible to attempt to suppress cough. |
|
| Urge-to-cough will be measured before treatment and three weeks following the final treatment session |
| Urge-to-Cough Testing: Cough Frequency | During UTC testing, participants are exposed to various scents and vocal and breathing tasks and the number of coughs elicited during and immediately following each task are counted. A cough frequency score for each testing session is the sum of the number of coughs counted during each task. Change in cough frequency is calculated by subtracting the baseline cough frequency from the 3 week post-treatment cough frequency. A negative score indicates cough frequency was less after treatment, which indicates an improvement. | Baseline and 3 weeks post-treatment |
| BG001 | Sub-threshold Capsaicin | Participants will be exposed repeatedly to a single sub-threshold dose of aerosolized capsaicin through a nebulizer during treatment. This sub-threshold dose will elicit minimal or no urge-to-cough. Sub-threshold doses of diluted capsiacin via a KoKo Digidoser nebulizer: Participants will be repeatedly exposed to a sub-threshold dose of aerosolized capsaicin through the KoKo Digidoser nebulizer during treatment sessions. Participants will attend 6 treatment sessions and be given up to 12 exposures per treatment session. Participants will be encouraged to use cough suppression strategies outside of treatment sessions as much as possible to attempt to suppress cough. |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| Leicester Cough Questionnaire (LCQ) | The LCQ is a 19-item patient-report questionnaire that measures the impact of cough on quality of life. The questions are divided into Psychological, Physical, and Social subscales which are an average of the questions that make up each subscale. The range for each subscale is 1-7. The subscale scores are summed to get a total LCQ score, which can range from 3-21. A higher score indicates less impact on quality of life. | Mean | Standard Deviation | units on a scale |
|
| Urge-to-cough (UTC) test: UTC sum | During UTC testing, participants are exposed to various scents and various vocal and breathing tasks (12 tasks in total). After each task, they report the maximum UTC they felt during the task on a scale from 0 (no UTC) to 10 (maximum UTC). The UTC scores for each task are summed for a single score. This results in a possible UTC score of 0 (no UTC on any tasks) to 120 (maximum UTC on every task). | Mean | Standard Deviation | units on a scale |
|
| Urge-to-cough (UTC) test: cough frequency sum | During UTC testing, participants are exposed to various scents and complete various vocal and breathing tasks. They are instructed to let their body react naturally after each task and to NOT try to suppress their cough. The number of coughs elicited during each task is recorded. The final score is a sum of the cough frequency for each task. | Mean | Standard Deviation | sum cough frequency |
|
| OG001 | Sub-threshold Capsaicin | Participants will be exposed repeatedly to a single sub-threshold dose of aerosolized capsaicin through a nebulizer during treatment. This sub-threshold dose will elicit minimal or no urge-to-cough. Sub-threshold doses of diluted capsiacin via a KoKo Digidoser nebulizer: Participants will be repeatedly exposed to a sub-threshold dose of aerosolized capsaicin through the KoKo Digidoser nebulizer during treatment sessions. Participants will attend 6 treatment sessions and be given up to 12 exposures per treatment session. Participants will be encouraged to use cough suppression strategies outside of treatment sessions as much as possible to attempt to suppress cough. |
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| Secondary | Urge-to-Cough Testing | Urge-to-cough (UTC) testing involves presenting participants to various scents and vocal and breathing tasks (12 tasks in total) and asking them to rate their maximum perceived UTC on a scale from 0 (no UTC) to 10 (maximum UTC). The UTC score for each testing session is the sum of the the UTC scores from each individual task. This results in a possible score range from 0 (no UTC on any tasks) to 120 (score of 10 on every UTC task). UTC change is determined by subtracting the UTC score on each task at baseline from the UTC score for each task at 3 weeks post-treatment and then summing those scores. A negative UTC change score indicates the UTC score was lower post-treatment relative to baseline, which indicates an improvement. | Posted | Mean | Standard Deviation | units on a scale | Urge-to-cough will be measured before treatment and three weeks following the final treatment session |
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| Secondary | Urge-to-Cough Testing: Cough Frequency | During UTC testing, participants are exposed to various scents and vocal and breathing tasks and the number of coughs elicited during and immediately following each task are counted. A cough frequency score for each testing session is the sum of the number of coughs counted during each task. Change in cough frequency is calculated by subtracting the baseline cough frequency from the 3 week post-treatment cough frequency. A negative score indicates cough frequency was less after treatment, which indicates an improvement. | Posted | Mean | Standard Deviation | coughs | Baseline and 3 weeks post-treatment |
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| 0 |
| 11 |
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| 11 |
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| 11 |
| EG001 | Sub-threshold Capsaicin | Participants will be exposed repeatedly to a single sub-threshold dose of aerosolized capsaicin through a nebulizer during treatment. This sub-threshold dose will elicit minimal or no urge-to-cough. Sub-threshold doses of diluted capsiacin via a KoKo Digidoser nebulizer: Participants will be repeatedly exposed to a sub-threshold dose of aerosolized capsaicin through the KoKo Digidoser nebulizer during treatment sessions. Participants will attend 6 treatment sessions and be given up to 12 exposures per treatment session. Participants will be encouraged to use cough suppression strategies outside of treatment sessions as much as possible to attempt to suppress cough. | 0 | 8 | 0 | 8 | 0 | 8 |
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| D013568 | Pathological Conditions, Signs and Symptoms |