Back to resultsNeurophysiology of Cough Reflex Hypersensitivity (NOTCH)
Primary Purpose
Cough, Healthy Controls
Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Hydrochloric acid (0.15 molar)
Saline
Sponsored by
About this trial
This is an interventional basic science trial for Cough
Eligibility 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
Sites / Locations
- University Hospital of South Manchester
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Hydrochloric acid infusion
Saline
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Full Information
NCT ID
NCT00977366
First Posted
September 14, 2009
Last Updated
June 17, 2013
Sponsor
University of Manchester
Collaborators
JP Moulton Charitable Foundation, Medical Research Council
1. Study Identification
Unique Protocol Identification Number
NCT00977366
Brief Title
Neurophysiology of Cough Reflex Hypersensitivity
Acronym
NOTCH
Official Title
Pilot Study Investigating Central Sensitisation of the Cough Reflex in Subjects With Chronic Cough and Healthy Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
February 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Manchester
Collaborators
JP Moulton Charitable Foundation, Medical Research Council
4. Oversight
Data Monitoring Committee
No
5. Study Description
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:
Can the investigators induce temporary central sensitisation of the cough reflex in healthy volunteers for testing of new medications?
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cough, Healthy Controls
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Hydrochloric acid infusion
Arm Type
Active Comparator
Arm Title
Saline
Arm Type
Placebo Comparator
Intervention Type
Other
Intervention Name(s)
Hydrochloric acid (0.15 molar)
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Saline
Intervention Description
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 Outcome Measure Information:
Title
Effect of oesophageal acid infusion on cough reflex sensitivity in chronic cough patients compared to healthy controls.
Description
Outcome measures include; cough reflex sensitivity, pain threshold measures, 24 hour objective cough rate
Time Frame
baseline, immediatley after infusion, 90 minutes post infusion, 180 minutes post infusion, 24 hours after baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ashley Woodcock, Prof
Organizational Affiliation
the University of Manchester
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital of South Manchester
City
Manchester
ZIP/Postal Code
M23 9LT
Country
United Kingdom
12. IPD Sharing Statement
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Neurophysiology of Cough Reflex Hypersensitivity
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