Abuse Liability of Pregabalin and Its Effects on Benzodiazepine Withdrawal Symptoms

Evaluation of Pregabalin's Abuse Liability and Its Effects on Benzodiazepine Withdrawal Symptoms in Inpatients Undergoing Medically Assisted Benzodiazepine Withdrawal

The purpose of this study is to determine if a single dose of pregabalin 300mg in patients receiving medications for sedative-hypnotic withdrawal symptoms will produce meaningful differences in measures of "drug liking" and "drug high" as compared to placebo.

Study Overview

• Status: Terminated
• Conditions: Substance-Related Disorders
• Intervention / Treatment: Drug: Pregabalin; Drug: Placebo

Detailed Description

Pregabalin is currently being explored as a pharmacotherapy for substance use disorders. Open-labeled, uncontrolled studies indicate modest efficacy of pregabalin in benzodiazepine withdrawal symptom management and as a long-term benzodiazepine dependence treatment. Concurrently, there is increasing information from case reports and adverse drug event registries regarding pregabalin abuse in patients with substance use disorders.

Given that the abuse liability of pregabalin has not been clearly established, nor its effects on benzodiazepine withdrawal symptoms in inpatients, this study is a randomized, double-blind, placebo-controlled, cross-over, abuse liability study of a single dose of pregabalin 300mg, nested within a randomized,double-blind placebo-controlled, feasibility study evaluating pregabalin's effects on withdrawal symptoms in inpatients undergoing medically-assisted withdrawal from benzodiazepine, zopiclone or zolpidem.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5S 3M2
      • Centre for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Admitted to the Medical Withdrawal Unit at the Centre for Addiction and Mental Health for medically assisted withdrawal from benzodiazepines, zopiclone and/or zolpidem
• Willing and capable to give written informed consent

Exclusion Criteria:

• Patients who are hypersensitive to pregabalin or to any ingredient in the formulation or component of the container.
• Pregnant or nursing women
• Renal impairment (creatinine clearance less than 60ml/min)
• History of angioedema, or taking drugs associated with angioedema (e.g., ACE-inhibitors).
• Currently taking pregabalin or gabapentin
• Currently taking thiazolidinedione antidiabetic agents (e.g., rosiglitazone, pioglitazone)
• Previous history of pregabalin or gabapentin abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pregabalin; Pregabalin titrated up to, and tapered from, 225mg/day in divided doses for 10 days	Drug: Pregabalin; In replacement of their morning 75mg pregabalin or placebo dose on Days 6 and 8, all participants will receive either a single dose of 300mg of pregabalin or placebo, in a randomized, double-blind, crossover manner. This is when steady state concentrations of pregabalin occur.; Other Names: Lyrica; Drug: Placebo; In replacement of their morning 75mg pregabalin or placebo dose on Days 6 and 8, all participants will receive either a single dose of 300mg of pregabalin or placebo, in a randomized, double-blind, crossover manner. This is when steady state concentrations of pregabalin occur.
Placebo Comparator: Placebo; Placebo for 10 days	Drug: Pregabalin; In replacement of their morning 75mg pregabalin or placebo dose on Days 6 and 8, all participants will receive either a single dose of 300mg of pregabalin or placebo, in a randomized, double-blind, crossover manner. This is when steady state concentrations of pregabalin occur.; Other Names: Lyrica; Drug: Placebo; In replacement of their morning 75mg pregabalin or placebo dose on Days 6 and 8, all participants will receive either a single dose of 300mg of pregabalin or placebo, in a randomized, double-blind, crossover manner. This is when steady state concentrations of pregabalin occur.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline on Visual Analogue Scale for "Drug Liking" over 5 hours post-dose administration	On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Profile of Mood States (POMS)		On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Psychomotor Performance (Digit Symbol Substitution Test (DSST)	Digit Symbol Substitution Test (DSST)	On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Visual Analogue Scale for "Take Drug Again"		On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Visual Analogue Scale for "Any Drug Effects"		On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Visual Analogue Scale for "Good Effects"		On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Visual Analogue Scale for "Bad Effects"		On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Visual Analogue Scale for "Feel Sick"		On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Visual Analogue Scale for "Nausea"		On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Visual Analogue Scale for "Sleepy"		On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Visual Analogue Scale for "Dizzy"		On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Sedation (Addiction Research Center Inventory (ARCI)	Addiction Research Center Inventory (ARCI)	On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Euphoria (Addiction Research Center Inventory (ARCI)	Addiction Research Center Inventory (ARCI)	On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Dysphoric Changes (Addiction Research Center Inventory (ARCI)	Addiction Research Center Inventory (ARCI)	On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Psychotomimetic Changes (Addiction Research Center Inventory (ARCI)	Addiction Research Center Inventory (ARCI)	On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Somatic Disturbances (Addiction Research Center Inventory (ARCI)	Addiction Research Center Inventory (ARCI)	On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Sensory Disturbances (Addiction Research Center Inventory (ARCI)	Addiction Research Center Inventory (ARCI)	On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Tmax Estimated peak plasma pregabalin concentration	Estimated peak plasma pregabalin concentration	On Days 6 and 8 only: obtained 1 hour post-dose
Change from baseline on Visual Analogue Scale for "Drug High" over 5 hours	Additional Primary Outcome	On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in score on the Benzodiazepine Withdrawal Symptom Questionnaire		Day 0, then twice daily on Days 1 to 10 (i.e., directly before 8am dose and 3pm)
Change in score on the six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI)		Day 0, then twice daily on Days 1 to 10 (i.e., directly before 8am dose and 3pm)
Clinical Global Impression Scale - Severity		Day 0
Clinical Global Impression Scale - Improvement		Day 10
Benzodiazepine use post-discharge	Assess benzodiazepine use since discharge	30 days post-discharge
Pregabalin use post-discharge	Assess pregabalin use since discharge	30 days post-discharge

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health

Publications and helpful links

Helpful Links

• The Centre for Addiction and Mental Health (CAMH) is the leading mental health and addictions research facility in Canada, and one of the largest in the world.

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: April 15, 2015
• First Submitted That Met QC Criteria: April 17, 2015
• First Posted (Estimate): April 22, 2015

Study Record Updates

• Last Update Posted (Estimate): March 23, 2016
• Last Update Submitted That Met QC Criteria: March 21, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Substance Withdrawal Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: 079-2014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided