Neurophysiology of Cough Reflex Hypersensitivity

Cough Clinical Trial

— NOTCH  

Official title:

Pilot Study Investigating Central Sensitisation of the Cough Reflex in Subjects With Chronic Cough and Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00977366
• Other study ID #: 09/H1004/21
• Status: Completed
• Phase: N/A
• First received: September 14, 2009
• Last updated: June 17, 2013
• Start date: March 2010
• Est. completion date: February 2013

Study information

• Verified date: June 2013
• Source: University of Manchester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: February 2013
• Est. primary completion date: September 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Cough
• Healthy Controls

Intervention

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.
• 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.

Locations

Country	Name	City	State
United Kingdom	University Hospital of South Manchester	Manchester

Sponsors (3)

Lead Sponsor	Collaborator
University of Manchester	J P Moulton Charitable Foundation, Medical Research Council

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No