Substance-Related Disorders
Conditions
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.
Interventions
DRUGPregabalin
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.
DRUGPlacebo
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.
Sponsors
Centre for Addiction and Mental Health
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Dysphoric Changes (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 | Addiction Research Center Inventory (ARCI) |
| Psychotomimetic Changes (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 | Addiction Research Center Inventory (ARCI) |
| Somatic Disturbances (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 | Addiction Research Center Inventory (ARCI) |
| Sensory Disturbances (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 | Addiction Research Center Inventory (ARCI) |
| Tmax Estimated peak plasma pregabalin concentration | On Days 6 and 8 only: obtained 1 hour post-dose | Estimated peak plasma pregabalin concentration |
| Change from baseline on Visual Analogue Scale for Drug High over 5 hours | On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose | Additional Primary Outcome |
| 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) | On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose | Digit Symbol Substitution Test (DSST) |
| 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 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) | On Days 6 and 8 only: Baseline (0), and at 1, 2, 2.5, 3, 4, 5 hours post-dose | Addiction Research Center Inventory (ARCI) |
| Euphoria (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 | Addiction Research Center Inventory (ARCI) |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 | 30 days post-discharge | Assess benzodiazepine use since discharge |
| Pregabalin use post-discharge | 30 days post-discharge | Assess pregabalin use since discharge |
Countries
Canada
Outcome results
None listed