Gabapentin Treatment of Benzodiazepine Dependence

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01893632
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arms: 2
• Actual Duration (Months): 33
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Benzodiazepine Dependence	Drug: gabapentin; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Gabapentin Treatment of Benzodiazepine Dependence
• Actual Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: gabapentin; Other Names: Neurontin
Placebo Comparator: Placebo Capsules filled with riboflavin.	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Abstinence From Benzodiazepine Use [last two weeks of 12 week trial]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	John Mariani	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Study Website

Publications

None provided.

• Responsible Party: John Mariani MD, Assistant Professor of Clinical Psychiatry, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT01893632
• Other Study ID Numbers: 6740
• First Posted: Jul 9, 2013
• Last Update Posted: Apr 24, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by John Mariani MD, Assistant Professor of Clinical Psychiatry, New York State Psychiatric Institute: Benzodiazepines; clonazepam; alprazolam; Klonopin; Xanax; diazepam; Valium; lorazepam; Ativan
• Additional relevant MeSH terms: Gabapentin

Study Results

Participant Flow

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description	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. gabapentin	Capsules filled with riboflavin. Placebo
Period Title: Overall Study
STARTED	1	1
COMPLETED	1	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Gabapentin	Placebo	Total
Arm/Group Description	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. gabapentin	Capsules filled with riboflavin. Placebo	Total of all reporting groups
Overall Participants	1	1	2
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59 (0)	59 (0)	59 (0)
Sex: Female, Male (Count of Participants)
Female	0 0%	1 100%	1 50%
Male	1 100%	0 0%	1 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 100%	1 50%
Not Hispanic or Latino	1 100%	0 0%	1 50%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	1 100%	0 0%	1 50%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 100%	1 50%

Outcome Measures

1. Primary Outcome

Title	Abstinence From Benzodiazepine Use
Description	Achievement of two weeks abstinence from benzodiazepine use at end of trial
Time Frame	last two weeks of 12 week trial

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description	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. gabapentin	Capsules filled with riboflavin. Placebo
Measure Participants	1	1
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	12 weeks of trial
Arm/Group Title	Gabapentin		Placebo
Arm/Group Description	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. gabapentin		Capsules filled with riboflavin. Placebo
All Cause Mortality
	Gabapentin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Serious Adverse Events
	Gabapentin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Gabapentin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/1 (100%)
Gastrointestinal disorders
appetite change	0/1 (0%)	0	1/1 (100%)	1
nausea	0/1 (0%)	0	1/1 (100%)	1
General disorders
anxiety	0/1 (0%)	0	1/1 (100%)	1
chest tightness	0/1 (0%)	0	1/1 (100%)	1
confusion	1/1 (100%)	1	0/1 (0%)	0
sensory overstimulation	0/1 (0%)	0	1/1 (100%)	1
Musculoskeletal and connective tissue disorders
unsteady gait	1/1 (100%)	1	0/1 (0%)	0
coordination issues	1/1 (100%)	1	0/1 (0%)	0

Limitations/Caveats

due to poor recruitment, enrollment was limited to two participants and trial was terminated.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.