Neurophysiology and Pharmacology of Cough Reflex Hypersensitivity

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.

Study Overview

• Status: Completed
• Conditions: Chronic Cough
• Intervention / Treatment: Drug: ketamine

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M23 9LT
    • University of Manchester, Education and Research Centre, Wythenshawe Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cough Reflex Sensitivity	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Upper Oesophageal Pain Thresholds	6 months
Pain Thresholds Pharynx	6 months
Pain Thresholds Chest Wall	6 months

Collaborators and Investigators

• Sponsor: Jacky Smith

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: March 9, 2009
• First Submitted That Met QC Criteria: March 9, 2009
• First Posted (Estimate): March 10, 2009

Study Record Updates

• Last Update Posted (Estimate): June 19, 2013
• Last Update Submitted That Met QC Criteria: June 17, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Cough; NMDA receptor; Cough reflex; central sensitisation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Hypersensitivity; Cough; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 07/H1004/142