Gabapentin Treatment of Benzodiazepine Dependence

• ClinicalTrials.gov Identifier: NCT01893632
• Recruitment Status: Terminated
• First Posted: July 9, 2013
• Results First Posted: July 24, 2018
• Last Update Posted: April 24, 2019
• Sponsor: New York State Psychiatric Institute
• Information provided by (Responsible Party): John Mariani MD, New York State Psychiatric Institute

Tracking Information

• First Submitted Date: June 29, 2013
• First Posted Date: July 9, 2013
• Results First Submitted Date: June 27, 2018
• Results First Posted Date: July 24, 2018
• Last Update Posted Date: April 24, 2019
• Actual Study Start Date: July 2013
• Actual Primary Completion Date: April 1, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 27, 2018)

Abstinence From Benzodiazepine Use [ Time Frame: last two weeks of 12 week trial ]

Achievement of two weeks abstinence from benzodiazepine use at end of trial

Original Primary Outcome Measures (submitted: July 2, 2013)

Abstinence From Benzodiazepine Use [ Time Frame: 12 weeks ]

Achievement of two weeks abstinence from benzodiazepine use

• Change History: Complete list of historical versions of study NCT01893632 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Gabapentin Treatment of Benzodiazepine Dependence
• Official Title: Gabapentin Treatment of Benzodiazepine Dependence
• Brief Summary: Benzodiazepine dependence is a growing public health problem for which very few evidenced-based treatment approaches are available. Approximately 683,000 individuals met past year criteria for sedative-hypnotic use disorders in the US during 2010, a prevalence greater than heroin or methamphetamine dependence. The most commonly prescribed sedative-hypnotic agents are the benzodiazepines. Chronic use induces pharmacodynamic tolerance in the GABA neurotransmitter system and individuals with physiological dependence find benzodiazepines difficult to discontinue because of withdrawal or rebound symptoms, which include autonomic arousal, depression, anxiety, and insomnia. Available evidence-based treatment approaches have been primarily directed at therapeutic users of benzodiazepines who do not meet criteria for a substance use disorder, with a general consensus that the gradual taper of benzodiazepines over a period of several months is the optimal approach. However, patients with benzodiazepine dependence are typically referred for inpatient detoxification treatment, which rapidly tapers patients off benzodiazepines. Protracted withdrawal symptoms frequently persist after discharge, predisposing patients to relapse. More effective pharmacotherapeutic strategies are needed for the treatment of benzodiazepine dependence in the outpatient setting.

Detailed Description

Gabapentin has proven to be a safe and well-tolerated medication with a low abuse liability, thereby making it ideal for use in the outpatient setting.

The proposed Exploratory Development research project is a double-blind randomized controlled clinical trial comparing the efficacy of gabapentin to placebo for the outpatient treatment of benzodiazepine dependence. The goal of this project is to study the effects of gabapentin on the participants' benzodiazepine use in a facilitated taper-to-abstinence model, where participants will be actively using benzodiazepines at study entry, gabapentin treatment will be introduced, and participants will be counseled to gradually discontinue benzodiazepine use over the study period while gabapentin treatment is maintained. A modified version of Medical Management will be used to facilitate compliance with study medication and other study procedures, and includes clinical instruction for gradually reducing benzodiazepine use 25% per week. Benzodiazepines are not prescribed in the proposed study; participants continue to obtain benzodiazepines from their own prescribed or nonprescribed sources.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Benzodiazepine Dependence

Intervention

• Drug: gabapentin
  Other Name: Neurontin
• Drug: Placebo

Study Arms

• Experimental: Gabapentin
  All study medication will be over-capsulated with riboflavin to assess compliance using quantitative fluoroscopy. All participants will take three capsules three times per day throughout the study period. During week 1, GBP will be titrated over a five-day period to the dose target (GBP 1200 mg three times daily) or the maximum tolerated dose. Medication dosing will continue at GBP 1200 mg three times daily or placebo through the end of the study period (week 12). Dose reductions will be made for tolerability if necessary.
  Intervention: Drug: gabapentin
• Placebo Comparator: Placebo
  Capsules filled with riboflavin.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 20, 2018): 2
• Original Estimated Enrollment (submitted: July 2, 2013): 50
• Actual Study Completion Date: April 1, 2016
• Actual Primary Completion Date: April 1, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Meets DSM-IV-TR criteria for BZD dependence
2. Using BZDs a minimum of 5 days per week over the past 28 days
3. Between the ages of 18 and 60
4. Able to provide informed consent

Exclusion Criteria:

1. Any current DSM-IV-TR Axis I psychiatric disorder, other than BZD dependence, that might require intervention over the course of the study, including schizophrenia, bipolar disorder, major depressive disorder or panic disorder.
2. Receiving psychotropic medication other than BZDs
3. Evidence of physiological BZD withdrawal (pulse > 100; blood pressure > 140/90)
4. History of BZD withdrawal seizures or withdrawal delirium
5. History of allergic reaction to GBP
6. Pregnancy, lactation, or failure in female patients to use adequate contraceptive methods
7. Unstable physical disorders which might make participation hazardous medical history
8. Subjects who have a current DSM-IV-TR diagnosis of other substance dependence, with the exception of nicotine and caffeine history; dependence

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01893632
• Other Study ID Numbers: 6740
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: John Mariani MD, New York State Psychiatric Institute
• Study Sponsor: New York State Psychiatric Institute
• Collaborators: Not Provided

Investigators

• Principal Investigator: John J. Mariani, MD; New York State Psychiatric Institute

• PRS Account: New York State Psychiatric Institute
• Verification Date: April 2019