Cough Desensitization Therapy for Cough Hypersensitivity Syndrome

NCT04256733 | Completed Early Phase 1 Results FDA Drug

• 1 other identifier: 188-88
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Cough

Keywords

chronic cough; refractory chronic cough; cough hypersensitivity syndrome

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Urge-to-Cough Testing

  Urge-to-cough will be measured before treatment and three weeks following the final treatment session

• Urge-to-Cough Testing: Cough Frequency

  Baseline and 3 weeks post-treatment

Study Arms (2)

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.

Biological: Supra-threshold and progressive doses of diluted capsaicin via a Koko Digidoser nebulizer

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.

Biological: Sub-threshold doses of diluted capsiacin via a KoKo Digidoser nebulizer

Interventions

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.

Supra-threshold capsaicin

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.

Sub-threshold capsaicin

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Under 18 years of age
• Currently a smoker of any substance
• Pregnant or attempting to become pregnant
• Diagnosed with a respiratory or pulmonary condition (e.g., asthma, COPD, emphysema, lung cancer, bronchitis)
• 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

Sponsors & Collaborators

• University of Montana: lead

Study Sites (1)

University of Montana

Missoula, Montana, 59812, United States

Location

Related Publications (1)

• 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: 35091204 DERIVED

MeSH Terms

Conditions

Cough; Chronic Cough; cough hypersensitivity syndrome

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Laurie Slovarp
• Organization: University of Montana

laurie.slovarp@umontana.edu

406-243-2107

Study Officials

• Laurie J Slovarp, PhD

  University of Montana

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and outcome assessors will be blinded to group assignment (active treatment vs placebo).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: One group will receive the placebo treatment while the second group receives the active treatment.

Study Record Dates

• First Submitted: September 24, 2019
• First Posted: February 5, 2020
• Study Start: May 1, 2019
• Primary Completion: November 30, 2020
• Study Completion: February 13, 2021
• Last Updated: March 4, 2024
• Results First Posted: March 4, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)