Neurophysiology and Pharmacology of Cough Reflex Hypersensitivity

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jacky Smith, University of Manchester
ClinicalTrials.gov Identifier:
NCT00858624
First received: March 9, 2009
Last updated: June 17, 2013
Last verified: June 2013
  Purpose

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 (Subject, 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Upper Oesophageal Pain Thresholds [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Pain Thresholds Pharynx [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Pain Thresholds Chest Wall [ Time Frame: 6 months ] [ Designated as safety issue: No ]

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00858624

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

No publications provided

Responsible Party: Jacky Smith, Reader, University of Manchester
ClinicalTrials.gov Identifier: NCT00858624     History of Changes
Other Study ID Numbers: 07/H1004/142
Study First Received: March 9, 2009
Last Updated: June 17, 2013
Health Authority: United Kingdom: National Health Service
United Kingdom: Research Ethics Committee

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

Additional relevant MeSH terms:
Cough
Hypersensitivity
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Immune System Diseases
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014