Efficacy of Pregabalin on Chronic Cough

Sponsor

Ottawa Hospital Research Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT02482818

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Sep 1, 2015

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Dec 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 Names: 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.

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 Names:

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

Determine the impact of pregabalin on a cough specific quality of life questionnaire (Leicester Cough Questionnaire) [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

Evaluate the impact of pregabalin on cough reflex sensitivity, which can be objectively measured using citric acid cough challenge [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

Criteria

Ages Eligible for Study:

18 Years to 84 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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