Clinical trial NCT02423018: Abuse Liability of Pregabalin and Its Effects on Benzodiazepine Withdrawal Symptoms
Official title: Evaluation of Pregabalin's Abuse Liability and Its Effects on Benzodiazepine Withdrawal Symptoms in Inpatients Undergoing Medically Assisted Benzodiazepine Withdrawal
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Substance-Related Disorders
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
First posted: 2015-04-22
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline on Visual Analogue Scale for "Drug Liking" over 5 hours post-dose administration
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Secondary outcomes:
measure: Profile of Mood States (POMS)
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Psychomotor Performance (Digit Symbol Substitution Test (DSST)
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Visual Analogue Scale for "Take Drug Again"
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Visual Analogue Scale for "Any Drug Effects"
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Visual Analogue Scale for "Good Effects"
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Visual Analogue Scale for "Bad Effects"
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Visual Analogue Scale for "Feel Sick"
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Visual Analogue Scale for "Nausea"
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Visual Analogue Scale for "Sleepy"
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Visual Analogue Scale for "Dizzy"
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Sedation (Addiction Research Center Inventory (ARCI)
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Euphoria (Addiction Research Center Inventory (ARCI)
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Dysphoric Changes (Addiction Research Center Inventory (ARCI)
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Psychotomimetic Changes (Addiction Research Center Inventory (ARCI)
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Somatic Disturbances (Addiction Research Center Inventory (ARCI)
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Sensory Disturbances (Addiction Research Center Inventory (ARCI)
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
measure: Tmax Estimated peak plasma pregabalin concentration
timeFrame: On Days 6 and 8 only: obtained 1 hour post-dose
measure: Change from baseline on Visual Analogue Scale for "Drug High" over 5 hours
timeFrame: On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose
Other outcomes:
measure: Change in score on the Benzodiazepine Withdrawal Symptom Questionnaire
timeFrame: Day 0, then twice daily on Days 1 to 10 (i.e., directly before 8am dose and 3pm)
measure: Change in score on the six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI)
timeFrame: Day 0, then twice daily on Days 1 to 10 (i.e., directly before 8am dose and 3pm)
measure: Clinical Global Impression Scale - Severity
timeFrame: Day 0
measure: Clinical Global Impression Scale - Improvement
timeFrame: Day 10
measure: Benzodiazepine use post-discharge
timeFrame: 30 days post-discharge
measure: Pregabalin use post-discharge
timeFrame: 30 days post-discharge
Locations:
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Centre for Addiction and Mental Health
name: Beth Sproule, PharmD
role: PRINCIPAL_INVESTIGATOR
References: