GHB Withdrawal Symptoms and Effectiveness of Treatment With Lorazepam Versus Pentobarbital - 1

Condition(s) targeted: Sodium Oxybate; Substance-Related Disorders

Intervention: Lorazepam (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: National Institute on Drug Abuse (NIDA)

Official(s) and/or principal investigator(s):
Karen Miotto, M.D., Principal Investigator, Affiliation: University of California, Los Angeles

Gamma hydroxybutyrate (GHB) is a powerful central nervous system depressant. The number of individuals seeking treatment for GHB abuse has been steadily increasing in the United States. Currently, lorazepam and pentobarbital are two medications used to treat individuals who experience GHB-withdrawal symptoms. The purpose of this study is to describe the signs and symptoms of GHB withdrawal and to identify predictors of withdrawal severity. The study will also evaluate the safety and effectiveness of treatment with lorazepam versus pentobarbital for GHB detoxification.

Official title: GHB: Effects, Withdrawal and Treatment

Study design: Treatment, Randomized, Single Blind, Uncontrolled, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Subjective withdrawl symptoms measures, Days 1 through 14

Detailed description: GHB and GHB precursors such as 1,4-butanediol and gamma-butylrolactone (GBL) have become popular drugs of abuse. In cases of severe withdrawal, delirium, confusion, hallucinations, and agitation can occur. There has been a sharp rise in the number of GHB related emergency room visits over the past few years, yet little is known about the effective treatment of GHB withdrawal and dependence. The purpose of this study is to describe the signs and symptoms of GHB withdrawal, identify predictors of withdrawal severity, and evaluate the safety and effectiveness of treatment for GHB detoxification. There will be compensation for screening assessments.

The study includes two phases. The open-label Phase 1 will aim to determine the safety of lorazepam for the treatment of mild GHB withdrawal. Participants who progress into moderate or severe withdrawal will enter the controlled Phase 2. In Phase 2, participants will be randomly assigned to receive either lorazepam or pentobarbital in order to determine which drug is more effective in treating GHB withdrawal.

The study will consist of 1 to 2 outpatient screening visits, followed by up to 15 days of inpatient detoxification treatment and assessment. After hospital discharge from inpatient treatment, measures of protracted GHB withdrawal and psychiatric symptoms will be obtained on an outpatient weekly basis for 8 weeks. Repeat measures of cognitive functioning will be obtained at baseline, termination of treatment, and at 30, 60, and 90-day follow-up intervals in order to assess long-term neurocognitive effects of GHB withdrawal and use.

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Meets DSM-IV criteria for GHB dependence

- Self-reported as GHB dependent with current daily use of GHB

- Use of GHB for at least 20 consecutive days prior to enrollment

- Desire to stop GHB use

- Availability of a friend or family member to act as a collateral informant

- Speaks and understands English

Exclusion Criteria:

- Females who are pregnant, breastfeeding, or do not agree to use adequate forms of

contraception

- History of seizures

- A baseline EEG of clinical concern that requires inpatient ICU detoxification

- Any anticonvulsant therapy during the 3 years prior to enrollment

- Pancreatic disease, such as insulin-dependent diabetes

- Liver disease that requires medication or medical treatment

- Gastrointestinal or kidney disease that might significantly impair absorption,

metabolism, or excretion of study drug, or might require medication or medical treatment

- Asthma, hives, angioedema, or similar condition

- Acute intermittent porphyria or porphyria variegata

- Neurological or psychiatric disorders, including psychosis, bipolar disorder, or other

disorders that require treatment or might make study compliance difficult (assessed by the Structured Clinical Interview for DSM-IV-TR)

- Positive tuberculosis (PPD) skin test with a clinical history and chest X-ray

indicative of active tuberculosis (individuals with a positive PPD test and a negative chest X-ray, who are not symptomatic for tuberculosis and do not require antituberculosis therapy, will be eligible to participate)

- Clinically significant abnormal baseline EKG

- Requirement for any of the following medications currently or within the 4 weeks prior

to enrollment: psychotropics (including sedatives/hypnotics, antidepressants, neuroleptics), prescription analgesics, anticonvulsants, antihypertensives, antiarrhythmics, or antiretroviral medications

- Nicotine dependent participants will be given nicotine patch therapy for the duration

of the study; participants who refuse nicotine patch therapy will continue in the study as determined by the hospital smoking and standard of care regulations

- Meets DSM-IV criteria for dependence on any psychoactive substance other than GHB,

caffeine, or nicotine

- Symptomatic HIV infection

- Alcohol breath test greater than .05 ppm at time of hospital admission

UCLA, Los Angeles, California 90095, United States; Recruiting
Karen Miotto, M.D., Phone: 310-206-2782, Email: kmiotto@mednet.ucla.edu

UCLA GHB Research Study

Starting date: August 2004
Last updated: January 12, 2007