Efficacy of Pregabalin on Chronic Cough

• ClinicalTrials.gov Identifier: NCT02482818
• Recruitment Status: Unknown
• First Posted: June 26, 2015
• Last Update Posted: September 25, 2020
• Sponsor: Ottawa Hospital Research Institute
• Information provided by (Responsible Party): Ottawa Hospital Research Institute

Study Description

Brief Summary:

The purpose of this study is to determine if Pregabalin, a medication used for the treatment of seizures and chronic pain, can be used to effectively treat people who suffer from non-asthmatic chronic cough (cough lasting over 8 weeks).

Condition or disease	Intervention/treatment	Phase
Cough	Drug: Pregabalin; Drug: Control-Placebo	Phase 1; Phase 2

Detailed Description:

A significant number of patients have an impaired quality of life due to chronic cough that fails to respond to therapeutic efforts.

Research suggests that patients with chronic cough may have an oversensitive cough reflex. Reflexes are involuntary responses to nerve stimulation. Since standard cough medicines may not be helpful for treating the oversensitive cough reflex, treatment with neurologically acting agents has been investigated.

Existing work in treatment of cough of unknown etiology has focused on the use of Gabapentin, a compound that acts neurologically that is used in the treatment of epilepsy and pain. A similar drug, Pregabalin, may be a superior medication for this indication. Pregabalin is rapidly absorbed with peak blood concentrations within 1 hour, has an approximate bioavailability of 90%, and is 3 to 10 times more potent than Gabapentin and has no known pharmacokinetic drug interactions.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy of Pregabalin on Chronic Cough: A Double Blind, Randomized Control Trial Comparing Pregabalin With Placebo in Patients With Non-asthmatic Chronic Cough
• Study Start Date: September 2015
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Control-Placebo; Administration of Placebo (Lactose instead of Pregabalin) pills in an increasing dose regimen followed by a decreasing dose regimen over 35 days during a 42 day trial. Initially an increasing dosage of placebo (Lactose) will be administered. On Visit 1 an increasing dose (25 mg twice a day for 3 days, then 50 mg twice a day for 2 days and then 75 mg twice a day for 2 days). Eight days after initial placebo administration, following an assessment by the Doctor of how well subjects are doing on their (drug or placebo), the study placebo will be increased to 100 mg twice a day. Twenty eight days after initial placebo administration subjects will begin to receive the study placebo in a reducing dose regimen for 7 days then follow up at day 42.	Drug: Control-Placebo; A control substance, Lactose is administered in place of Pregabalin.; Other Name: Lactose Pills.
Experimental: Pregabalin; Administration of Pregabalin in an increasing dose regimen followed by a decreasing dose regimen over 35 days during a 42 day trial. Initially an increasing dosage of Pregabalin will be administered. On Visit 1 an increasing dose (25 mg twice a day for 3 days, then 50 mg twice a day for 2 days and then 75 mg twice a day for 2 days). Eight days after initial medication administration, following an assessment by the Doctor of how well subjects are doing on the medication, the study medication will be increased to 100 mg twice a day. Twenty eight days after initial drug administration subjects will begin to receive the study medication in a reducing dose regimen for 7 days. Forty two days after initial drug administration the Doctor will meet with subjects to follow up.	Drug: Pregabalin; Increasing dose regimen depending on tolerability followed by decreasing dose regimen.

Outcome Measures

Primary Outcome Measures :

1. Determine the impact of pregabalin on a cough specific quality of life questionnaire (Leicester Cough Questionnaire) [ Time Frame: 42 days ]
   All patients will be required to fill out the questionnaire in the follow up visits. This questionnaire is validated, reliable and subjective method for assessing the response to therapy

Secondary Outcome Measures :

1. Evaluate the impact of pregabalin on cough reflex sensitivity, which can be objectively measured using citric acid cough challenge [ Time Frame: 42 days ]
   Citric acid has been used extensively in the literature as an effective inhaled compound that can induce cough. The changes in the concentration of citric acid that can cause 2 or 5 consecutive coughs (C2 or C5) has been used to objectively determine the impact of various therapies on cough receptors.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 84 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of non-asthmatic chronic cough defined as a cough experienced for a period of at least 8 weeks
• Negative methacholine challenge (within past year)
• Chest x-ray with absence of gross abnormality that could justify the cough or be a cause for the cough (within past 6 months)
• Male or female 18 years or older
• Willing and able to limit to 1 or less alcohol beverage per day (example: 360 ml of beer or 330 ml of cooler or 120 ml of wine)

Exclusion Criteria:

• Concurrent use of Gabapentin or Pregabalin for other indications (seizure disorder, chronic pain)
• History of allergy / intolerance or adverse effect with Gabapentin or Pregabalin.
• Concurrent use of central nervous system depressants (i.e. opioids or benzodiazepines)
• Not able to limit daily alcohol intake as recommended in the inclusion criteria
• Creatinine clearance < 60ml/min within past three months
• Current Smoker or has been quit less than 8 weeks
• Symptoms of post nasal drip
• History of gastroesophageal reflux. Only participants with untreated Gastroesophageal Reflux Disease (GERD) or less than 8 weeks of therapy will be excluded.
• Symptoms of upper airway cough syndrome
• ACE inhibitor use
• Allergy to citric acid
• Pregnant or nursing women
• History of angioedema or congestive heart failure

Contacts and Locations

Contacts

Contact: Kayvan Amjadi, MD; 613-798-5555 ext 18139; kamjadi@toh.on.ca

Contact: Nha Voduc, MD; 613-737-8899 ext 78198; nvoduc@toh.on.ca

Locations

Canada, Ontario

The Ottawa Hospital (General and Civic Campuses); Recruiting

Ottawa, Ontario, Canada, K1Y 4E9

Contact: Isabelle Seguin 613-737-8811 iseguin@ohri.ca

Principal Investigator: Kayvan Amjadi, MD

Sub-Investigator: Nha Voduc, MD

Sponsors and Collaborators

Ottawa Hospital Research Institute

Investigators

• Principal Investigator: Kayvan Amjadi, MD; Ottawa Hospital Research Institute

More Information

• Responsible Party: Ottawa Hospital Research Institute
• ClinicalTrials.gov Identifier: NCT02482818
• Other Study ID Numbers: 2011734-01H
• First Posted: June 26, 2015
• Last Update Posted: September 25, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Ottawa Hospital Research Institute:

chronic cough; cough hypersensitivity; Lyrica; Pregabalin; cough reflex sensitivity

Additional relevant MeSH terms:

Cough; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Pregabalin; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anticonvulsants; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs