Cough Desensitization Therapy for Cough Hypersensitivity Syndrome
Condition: Cough
MeSH terms: Cough; Hypersensitivity
Study type: Interventional
Phase: Early 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 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.
    

Intervention name(s): Supra-threshold and progressive doses of diluted capsaicin via a Koko Digidoser nebulizer; Sub-threshold doses of diluted capsiacin via a KoKo Digidoser nebulizer
Intervention type(s): Biological; Biological
Intervention description(s): 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.; 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.
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: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: chronic cough; refractory chronic cough; cough hypersensitivity syndrome