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Neurophysiology and Pharmacology of Cough Reflex Hypersensitivity

This study has been completed.
Information provided by (Responsible Party):
Jacky Smith, University of Manchester Identifier:
First received: March 9, 2009
Last updated: June 17, 2013
Last verified: June 2013

A cough lasting more than 2 months is known as a chronic cough, affecting 12-23% of the adult non-smoking population. Chronic cough has many associated complications including incontinence, muscular chest pains, blackouts and depression. Current treatment is often ineffective in these patients. To develop new medications the investigators need to understand more about the mechanisms that can lead to excessive coughing.

This study plans to compare a group of 12 healthy volunteers and 12 patients with a chronic cough. The investigators hypothesise that that chronic cough patients have a more sensitive cough reflex as a result central nervous system hyper-excitability (central sensitisation). The investigators will measure cough reflex sensitivity before and after administration of ketamine, a medication that blocks an important receptor in the central nervous system.

Condition Intervention
Chronic Cough
Drug: ketamine

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Health Services Research
Official Title: Neurophysiology and Pharmacology of Cough Reflex Hypersensitivity

Resource links provided by NLM:

Further study details as provided by University of Manchester:

Primary Outcome Measures:
  • Cough Reflex Sensitivity [ Time Frame: 6 months ]

Secondary Outcome Measures:
  • Upper Oesophageal Pain Thresholds [ Time Frame: 6 months ]
  • Pain Thresholds Pharynx [ Time Frame: 6 months ]
  • Pain Thresholds Chest Wall [ Time Frame: 6 months ]

Enrollment: 24
Study Start Date: February 2008
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Chronic Cough Patients Drug: ketamine
Administration of low dose intravenous ketamine. Dose: 0.075mg/kg over 10 minutes followed by 0.005mg/kg/min over 20 minutes. Given as single infusion.
Active Comparator: Healthy Volunteers Drug: ketamine
Administration of low dose intravenous ketamine. Dose: 0.075mg/kg over 10 minutes followed by 0.005mg/kg/min over 20 minutes. Given as single infusion.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

Healthy Volunteers:

  • Over 18 years old
  • Measurable cough reflex sensitivity
  • No current or past history of chronic cough or chronic respiratory disease.
  • No symptoms of gastro-oesophageal reflux disease, asthma or post-nasal drip.

Chronic Cough Patients

  • Over 18 years old
  • Chronic persistent cough (> 8 weeks) despite investigation and/or treatment trials for cough variant asthma/post nasal drip and gastro-oesophageal reflux disease.
  • Normal CXR
  • Normal lung function
  • Measurable cough reflex sensitivity

Exclusion Criteria:

  • Recent Upper Respiratory Tract Infection (4 weeks)
  • Pregnancy/breast feeding
  • Current smokers or ex-smokers with < 6 months abstinence or cumulative history of > 10 packyears
  • Diabetes Mellitus
  • Opiate or ACE Inhibitor use.
  • Any centrally acting medication which has the potential to alter cough reflex sensitivity.
  • Significant and ongoing chronic respiratory, cardiovascular (in particular hypertension), gastro-intestinal, haematological (porphyria), neurological or psychiatric illness.
  • Drug or alcohol abuse
  • History of allergy or reaction to ketamine of other NMDA receptor antagonists.
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Please refer to this study by its identifier: NCT00858624

United Kingdom
University of Manchester, Education and Research Centre, Wythenshawe Hospital
Manchester, United Kingdom, M23 9LT
Sponsors and Collaborators
Jacky Smith
  More Information

Responsible Party: Jacky Smith, Reader, University of Manchester Identifier: NCT00858624     History of Changes
Other Study ID Numbers: 07/H1004/142
Study First Received: March 9, 2009
Last Updated: June 17, 2013

Keywords provided by University of Manchester:
Cough reflex
NMDA receptor
central sensitisation

Additional relevant MeSH terms:
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Immune System Diseases
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action processed this record on May 23, 2017