Cough Desensitization Therapy for Cough Hypersensitivity Syndrome

• ClinicalTrials.gov Identifier: NCT04256733
• Recruitment Status: Completed
• First Posted: February 5, 2020
• Last Update Posted: March 2, 2021
• Sponsor: University of Montana
• Information provided by (Responsible Party): Laurie Slovarp, University of Montana

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cough	Biological: Supra-threshold and progressive doses of diluted capsaicin via a Koko Digidoser nebulizer; Biological: Sub-threshold doses of diluted capsiacin via a KoKo Digidoser nebulizer	Early Phase 1

Detailed Description:

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).

1. Cough sensitivity testing: Standardized procedures that have been established and approved by the FDA will be used to determine cough sensitivity. Participants will inhale capsaicin vapor (a known cough stimulant) through a nebulizer with dosimeter, that delivers a specific dose of capsaicin in a mist form. They will inhale doubling doses of capsaicin mist from .49 micromolar to 1000 micromolar. The testing will be stopped when the investigators find the dose that causes five coughs or after giving the 1000 micromolar dose, whichever comes first. This testing will take approximately 30 minutes.
2. Urge-to-cough (UTC) testing: Participants be asked to report their UTC on a scale from 0 (no UTC) to 10 (maximum UTC) after each mist of capsaicin and after being presented with the following stimulants/tasks that cause some people to cough: perfume, bleach, vinegar, wood chips, laundry soap, cleaning wipe, deep and fast breath through the mouth, sustained voicing, reading a 55 word passage, and yelling a short phrase). This testing will take about 10 minutes.
3. Cough-related quality of life: Participants will complete the Leicester Cough Questionnaire which is a 23-item validated questionnaire designed to measure cough-related quality of life. It will take about 5 minutes.
4. Cough suppression training. Participants will be trained in cough suppression strategies. These strategies include 1) relaxed throat breathing where they inhale quickly through the nose and exhale through tightly pursed lips, and 2) cough suppression swallow, which involves swallowing saliva or a sip of water with as much effort as possible and while pressing hands together tightly. This training will take approximately 15 minutes.
5. Cough frequency testing: Participants will carry a small audio recording device with a small microphone that attaches to the participant's shirt for 24 hours. The recording device will be in a small carrying case (about half the size of a typical cell phone) that can clip to a belt or waistband. Participants will return the recording device to the investigators at or before the first treatment visit (see below). The audio recording will be analyzed by computer software that counts the number of coughs in the 24-hour period. (NOTE: The audio recording will not be listened to by any PERSON and the recording will be deleted after it is analyzed by the computer software.)

(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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: One group will receive the placebo treatment while the second group receives the active treatment.
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: Participants and outcome assessors will be blinded to group assignment (active treatment vs placebo).
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Cough Reflex Desensitization for the Treatment of Cough Hypersensitivity Syndrome
• Actual Study Start Date: May 1, 2019
• Actual Primary Completion Date: November 30, 2020
• Actual Study Completion Date: February 13, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Biological: 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.
Placebo Comparator: 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.	Biological: 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.

Outcome Measures

Primary Outcome Measures :

1. Change in Leicester Cough Questionnaire scores [ Time Frame: The LCQ will be measured before treatment and three weeks following treatment ]
   Change in cough-related quality of life will be measured with the Leicester Cough Questionnaire (LCQ). The LCQ is a 23-item validated patient-report questionnaire that takes about 5 minutes to fill out. It results in three domain scores (Social, Psychological, and Physical) and one Total score, which is the sum of the domain scores. Domain scores are between 1 and 7. The total score is between 3 and 21. A higher score means a better outcome.

Secondary Outcome Measures :

1. Change in cough sensitivity [ Time Frame: Cough sensitivity will be measured before treatment and three weeks following the final treatment session ]
   Change in cough sensitivity will be measured with cough challenge testing before and after treatment. Standardized procedures that have been established and approved by the FDA will be used. Participants will inhale capsaicin vapor (a known cough stimulant) through a nebulizer with dosimeter, that delivers a specific dose of capsaicin in a mist form. They will inhale doubling doses of capsaicin mist from .49 micromolar to 1000 micromolar. The testing will be stopped when the investigators find the dose that causes five coughs or after giving the 1000 micromolar dose, whichever comes first. This testing will take approximately 30 minutes.
2. Change in urge to cough testing [ Time Frame: Urge-to-cough will be measured before treatment and three weeks following the final treatment session ]
   Change in urge-to-cough testing will be measured by asking participants to report their urge-to-cough (UTC) on a scale from 0 (no UTC) to 10 (maximum UTC) after being presented with the following stimulants/tasks that cause some people to cough: perfume, bleach, cleaning solution, laundry soap, fabric softener, deep and fast breath through the mouth, sustained voicing, reading a 55 word passage, and yelling a short phrase. This testing will take about 10 minutes.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. At least 18 years of age
2. Currently suffering from a cough that started at least 8 weeks ago
3. Have seen at least one physician for the cough and have received medical treatment without success
4. Normal chest x-ray, pulmonary function testing, and laryngoscopy (laryngoscopy completed by your physician or the speech-language pathologist)
5. Have undergone behavioral cough suppression therapy without full resolution of cough
6. Willing to take a pregnancy test before enrollment (if applicable)
7. Willing to use contraception during the study (if applicable)
8. Willing to sign an informed consent form

Exclusion Criteria:

1. Under 18 years of age
2. Currently a smoker of any substance
3. Pregnant or attempting to become pregnant
4. Diagnosed with a respiratory or pulmonary condition (e.g., asthma, COPD, emphysema, lung cancer, bronchitis)
5. Taken any of the following medications within the past month: lisinopril/Prinivil/Zestril, captopril/Capoten, enalapril/Epaned/Asotec, ramipril/Altace, benazepril/Lotensin, fosinopril/Monopril, moexipril/Univasc, perindopril/Aceonm, quinapril/Accupril, trandolapril/Mavik

Contacts and Locations

Locations

United States, Montana

University of Montana

Missoula, Montana, United States, 59812

Sponsors and Collaborators

University of Montana

Investigators

• Principal Investigator: Laurie J Slovarp, PhD; University of Montana

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Laurie Slovarp, Associate Professor, University of Montana
• ClinicalTrials.gov Identifier: NCT04256733
• Other Study ID Numbers: 188-88
• First Posted: February 5, 2020
• Last Update Posted: March 2, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Laurie Slovarp, University of Montana:

chronic cough; refractory chronic cough; cough hypersensitivity syndrome

Additional relevant MeSH terms:

Cough; Hypersensitivity; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Immune System Diseases; Capsaicin; Antipruritics; Dermatologic Agents; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs