Cough Desensitization Therapy: Pilot 2

NCT05226299 | Completed Phase 1 FDA Drug

• 1 other identifier: UMontana
• Study Type: interventional
• Target: 22
• 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

Outcome Measures

Primary Outcomes (2)

• Change from baseline Leicester Cough Questionnaire (LCQ) score at 1 week post-treatment

  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.

  The LCQ will be measured before treatment (baseline) and 1 week post treatment

• Change from baseline visual analogue cough severity score at 1 week post-treatment

  Participant's perceived cough severity will be measured using a visual analogue scale. They will place a tick mark on a 100 mm line where 0mm indicates "no cough problem" and 100 mm indicates "worst possible cough problem".

  Cough severity will be will be measured before treatment (baseline) and 1 week post-treatment

Secondary Outcomes (2)

• Change from baseline cough-reflex sensitivity at 1 week post-treatment

  Cough-reflex sensitivity will be measured before treatment (baseline), and 1 week post-treatment

• Change from baseline urge-to-cough (UTC) testing at 1 week post-treatment

  UTC testing will be measured before treatment (baseline) and 1 week post-treatment

Study Arms (2)

Experimental: Supra-threshold capsaicin

EXPERIMENTAL

Arm: 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 dosimeter-controlled nebulizer

Arm: Placebo Comparator: Saline

PLACEBO COMPARATOR

Participants will be exposed repeatedly to aerosolized saline through a nebulizer during treatment.

Biological: Saline

Interventions

Supra-threshold and progressive doses of diluted capsaicin via a dosimeter-controlled nebulizer BIOLOGICAL

Participants will be exposured to increasing doses of aerosolized capsaicin (a known cough stimulant) through a dosimeter-controlled 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. Individual doses will never exceed 1000 micromolar. Cumulative doses per session will never exceed 2000 micromolar. Participants will attend 12 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.

Experimental: Supra-threshold capsaicin

Saline BIOLOGICAL

Participants will be repeatedly exposed to a saline through a dosimeter-controlled nebulizer during treatment sessions. Participants will attend 12 treatment sessions and be given up to 12 exposures per treatment session.

Arm: Placebo Comparator: Saline

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 (completed by your physician or a qualified speech-language pathologist).
• Completion of a laryngoscopy (by ENT physician or qualified speech-language pathologist) with no evidence of an anatomical abnormality (i.e., masses or lesions such as nodules, cysts, or cancer) that could contribute to cough.
• Willing to take a pregnancy test before enrollment (if applicable)
• Willing to use contraception during the study (if applicable; we will not be able to supply you with contraceptive methods)
• If you are diagnosed with asthma, you may enroll in the study if you are regularly followed by a pulmonologist who will verify, in writing, that your asthma symptoms are well-controlled (apart from cough symptoms) with your current medication protocol, which would not be altered when you are in the study. In order to remain in the study, your forced expiratory volume (FEV1), which will be measured during baseline lung function testing with spirometry, must be no less than 60% of predicted values given age, height, and weight. You must also carry a rescue inhaler with you when participating in all assessment and treatment sessions.
• Willing to sign an informed consent form

You may not qualify if:

• Under 18 years of age
• Positive for COVID-19 or presenting with any of the following symptoms of COVID- 19: fever or chills, sputum, difficulty breathing, fatigue, muscle or body aches, headache, loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, diarrhea.
• Have not followed current local, state, and CDC COVID-19 mitigation guidance, especially regarding travel.
• Unwilling to comply with COVID-19 precautions (see below)
• Currently a smoker of any substance
• Pregnant or attempting to become pregnant
• Diagnosed with a respiratory or pulmonary condition (other than asthma) that commonly contributes to cough (e.g., chronic obstructive pulmonary disease, emphysema, lung cancer, bronchitis)
• Diagnosed with asthma that is not well managed and/or do not have the necessary written consent by a pulmonologist to be in the study.
• Suffering from any signs of upper respiratory illness
• Taken any of the following medications within the past month:
• lisinopril/Prinivil/Zestril
• captopril/Capoten
• enalapril/Epaned/Asotec, ramipril/Altace
• benazepril/Lotensin
• fosinopril/Monopril

Sponsors & Collaborators

• University of Montana: lead

Study Sites (1)

University of Montana

Missoula, Montana, 59812, United States

Location

Related Publications (1)

• Slovarp LJ, Reynolds JE, Tolbert S, Campbell S, Welby S, Morkrid P. Cough desensitization treatment for patients with refractory chronic cough: results of a second pilot randomized control trial. BMC Pulm Med. 2023 Apr 28;23(1):148. doi: 10.1186/s12890-023-02423-6.

  PMID: 37118696 DERIVED

MeSH Terms

Conditions

Cough; Chronic Cough

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Laurie Slovarp, PhD

  University of Montana

  PRINCIPAL INVESTIGATOR

Study Design

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

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

Study Record Dates

• First Submitted: January 25, 2022
• First Posted: February 7, 2022
• Study Start: May 1, 2021
• Primary Completion: May 30, 2022
• Study Completion: August 30, 2022
• Last Updated: November 3, 2022

Record last verified: 2022-11

Locations

US (1)