Neurophysiology of Cough Reflex Hypersensitivity (NOTCH)

This study has been completed.
Sponsor:
Collaborators:
J P Moulton Charitable Foundation
Medical Research Council
Information provided by (Responsible Party):
Jacky Smith, University of Manchester
ClinicalTrials.gov Identifier:
NCT00977366
First received: September 14, 2009
Last updated: June 17, 2013
Last verified: June 2013
  Purpose

Central sensitisation is an increase in the excitability of nerves within the central nervous system, which can lead to heightened sensitivity to certain stimuli. This process is involved in some chronic pain conditions e.g. migraines and non−cardiac chest pain. Recent work by our group suggests central sensitisation may be an important mechanism leading to chronic cough.

The main questions in this study include:

  1. Can the investigators induce temporary central sensitisation of the cough reflex in healthy volunteers for testing of new medications?
  2. Can the investigators demonstrate exaggerated sensitisation in patients with chronic cough (indicating these patients are already centrally sensitised)?

In animal studies, acid infusion into the gullet (oesophagus) is able to induce central sensitisation of the cough reflex. Acid infusion into the oesophagus has also been shown to induce central sensitisation in human healthy volunteers, increasing the sensitivity to pain on the front of the chest but this study did not test the the cough reflex. Using human participants, the investigators plan to test whether acid infusion into the oesophagus increases the sensitivity of the cough reflex in healthy volunteers and also patients complaining of chronic cough.


Condition Intervention
Cough
Healthy Controls
Other: Hydrochloric acid (0.15 molar)
Other: Saline

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Pilot Study Investigating Central Sensitisation of the Cough Reflex in Subjects With Chronic Cough and Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by University of Manchester:

Primary Outcome Measures:
  • Effect of oesophageal acid infusion on cough reflex sensitivity in chronic cough patients compared to healthy controls. [ Time Frame: baseline, immediatley after infusion, 90 minutes post infusion, 180 minutes post infusion, 24 hours after baseline ] [ Designated as safety issue: No ]
    Outcome measures include; cough reflex sensitivity, pain threshold measures, 24 hour objective cough rate


Enrollment: 27
Study Start Date: March 2010
Study Completion Date: February 2013
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Hydrochloric acid infusion Other: Hydrochloric acid (0.15 molar)
Hydrochloric acid (0.15 molar) will be infused in to the lower oesophagus through a distal infusion port located at the tip of an oesophageal stimulation catheter.
Placebo Comparator: Saline Other: Saline
Normal saline will be infused in to the lower oesophagus through a distal infusion port located at the tip of an oesophageal stimulation catheter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Healthy volunteers inclusion:

  • Over 18 years
  • Measurable cough reflex sensitivity − required as is the primary end−point
  • No current or past history of chronic cough or chronic respiratory disease

Chronic Cough Patients inclusion:

  • Over 18 years
  • Chronic persistent cough (> 8 weeks) despite investigation and/or treatment trials for cough variant asthma/post−nasal drip and gastro−oesophageal reflux
  • Normal chest radiograph − primary respiratory cause for cough excluded
  • Normal lung function − primary respiratory cause for cough excluded Measurable cough reflex sensitivity − required as primary end−point

Exclusion Criteria:

  • Recent upper respiratory tract infection (<4 weeks) − this can lead to increased sensitivity of the cough reflex which resolves as the infection settles
  • Pregnancy/breast−feeding − unknown effects of oesophageal acid infusion
  • Current smokers or ex−smokers with < 6 month abstinence or history > 20 pack years − smoking can alter the sensitivity of the cough reflex
  • Opiate or ACE inhibitor use or centrally acting medication − can alter the cough reflex sensitivity
  • Symptomatic gastro−oesophageal reflux, post−nasal drip or asthma (chronic cough cohort may have been treated for these in the past but cough did not resolve) − these conditions are known to cause cough and alter cough reflex sensitivity
  • Significant ongoing chronic respiratory/cardiovascular/gastro−intestinal/haematological/ neurological/psychiatric illness. We are aiming to recruit healthy volunteers and chronic cough patients who are otherwise healthy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00977366

Locations
United Kingdom
University Hospital of South Manchester
Manchester, United Kingdom, M23 9LT
Sponsors and Collaborators
University of Manchester
J P Moulton Charitable Foundation
Medical Research Council
Investigators
Principal Investigator: Ashley Woodcock, Prof the University of Manchester
  More Information

No publications provided

Responsible Party: Jacky Smith, MRC Clinician Scientist/Honorary Respiratory Consultant, University of Manchester
ClinicalTrials.gov Identifier: NCT00977366     History of Changes
Other Study ID Numbers: 09/H1004/21
Study First Received: September 14, 2009
Last Updated: June 17, 2013
Health Authority: United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Cough
Hypersensitivity
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Immune System Diseases

ClinicalTrials.gov processed this record on July 29, 2014