Neurophysiology of Cough Reflex Hypersensitivity

NCT00977366 | Completed

• 1 other identifier: 09/H1004/21
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Cough; Healthy Controls

Outcome Measures

Primary Outcomes (1)

• Effect of oesophageal acid infusion on cough reflex sensitivity in chronic cough patients compared to healthy controls.

  Outcome measures include; cough reflex sensitivity, pain threshold measures, 24 hour objective cough rate

  baseline, immediatley after infusion, 90 minutes post infusion, 180 minutes post infusion, 24 hours after baseline

Study Arms (2)

Hydrochloric acid infusion

ACTIVE COMPARATOR

Other: Hydrochloric acid (0.15 molar)

Saline

PLACEBO COMPARATOR

Other: Saline

Interventions

Hydrochloric acid (0.15 molar) OTHER

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.

Hydrochloric acid infusion

Saline OTHER

Normal saline will be infused in to the lower oesophagus through a distal infusion port located at the tip of an oesophageal stimulation catheter.

Saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Manchester: lead
• JP Moulton Charitable Foundation: collaborator
• Medical Research Council: collaborator

Study Sites (1)

University Hospital of South Manchester

Manchester, M23 9LT, United Kingdom

Location

MeSH Terms

Conditions

Cough

Interventions

Hydrochloric Acid; 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)

Acids, Noncarboxylic; Acids; Inorganic Chemicals; Chlorine Compounds; Chlorides; Sodium Compounds

Study Officials

• Ashley Woodcock, Prof

  The University of Manchester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MRC Clinician Scientist/Honorary Respiratory Consultant

Study Record Dates

• First Submitted: September 14, 2009
• First Posted: September 15, 2009
• Study Start: March 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: February 1, 2013
• Last Updated: June 19, 2013

Record last verified: 2013-06

Locations

GB (1)