Neurophysiology of Cough Reflex Hypersensitivity (NOTCH)

June 17, 2013 updated by: Jacky Smith, University of Manchester

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
27

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Manchester, United Kingdom, M23 9LT
        • University Hospital of South Manchester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
baseline, immediatley after infusion, 90 minutes post infusion, 180 minutes post infusion, 24 hours after baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Manchester

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Medical Research Council
JP Moulton Charitable Foundation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ashley Woodcock, Prof, The University of Manchester

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2010

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2012

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 14, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 14, 2009

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 15, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 19, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 17, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 09/H1004/21

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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