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Completed

NCT Number: NCT00977366

Neurophysiology of Cough Reflex Hypersensitivity

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University Hospital of South Manchester

Manchester, M23 9LT, United Kingdom

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

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.

Primary outcomes

  1. 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

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

Sponsors and collaborators

Lead sponsor

University of Manchester

Other

Collaborators

  • JP Moulton Charitable Foundation
  • Medical Research Council

Registry information

Official study title

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

Acronym: NOTCH

Important dates

Study start
2010
Primary completion
2012
Study completion
2013
First posted
Sep 15, 2009
Registry last updated
Jun 19, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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