Cough Desensitization Therapy: Pilot 2
Condition: Cough
MeSH terms: Cough
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      The study will be a randomized, placebo-controlled, blinded study. It will take place in
      three phases, across 10 weeks.

      WEEK 1: BASELINE TESTING AND TRAINING (approximate time = 1 hour).

      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.

      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.

      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.

      Visual analogue cough severity (VAS): Participants will rate their cough severity on a visual
      analogue scale by placing a tick mark on a 100 mm line where 0 mm indicates "no cough" and
      100 mm indicates "worst possible cough".

      WEEKS 2-7: TREATMENT. Participants will attend treatment sessions twice per week for up to
      six weeks. Participants will use the breathing strategies following inhalation of either the
      active substance (experimental condition) or repeated exposures to an inactive substance
      (placebo condition). Participants will do this no more than twelve times per session. Each
      session will take 45-60 minutes. If a participant misses a treatment session, the
      investigators will attempt to re-schedule that session. Each participant must complete at
      least 10 treatment sessions to remain in the study.

      WEEKS 8 AND 10: POST-TREATMENT TESTING. Outcome measures, as in the baseline phase, will be
      taken at one-week and three-weeks post-treatment. The LCQ will be measured again at
      three-months post-treatment.
    

Intervention name(s): Supra-threshold and progressive doses of diluted capsaicin via a dosimeter-controlled nebulizer; Saline
Intervention type(s): Biological; Biological
Intervention description(s): 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.; 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.
Intervention MeSH terms: Capsaicin
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: Single (Participant)
Primary purpose: Treatment
Keywords: chronic cough; refractory chronic cough; cough hypersensitivity