Abuse Liability of Pregabalin and Its Effects on Benzodiazepine Withdrawal Symptoms

Substance-Related Disorders Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02423018
• Other study ID #: 079-2014
• Status: Terminated
• Phase: Phase 4
• First received: April 15, 2015
• Last updated: March 21, 2016
• Start date: April 2015
• Est. completion date: March 2016

Study information

• Verified date: March 2016
• Source: Centre for Addiction and Mental Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Substance-Related Disorders

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)	No
Other	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)	No
Other	Clinical Global Impression Scale - Severity		Day 0	No
Other	Clinical Global Impression Scale - Improvement		Day 10	No
Other	Benzodiazepine use post-discharge	Assess benzodiazepine use since discharge	30 days post-discharge	No
Other	Pregabalin use post-discharge	Assess pregabalin use since discharge	30 days post-discharge	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Tmax Estimated peak plasma pregabalin concentration	Estimated peak plasma pregabalin concentration	On Days 6 and 8 only: obtained 1 hour post-dose	No
Secondary	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	No

External 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.