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Benzodiazepine DependencePhase 2NCT00420771

Gabapentin Treatment of Benzodiazepine Abuse in Methadone Maintenance Patients

A Phase 2 study testing Gabapentin in people with Benzodiazepine Dependence and Opioid Dependence, run by New York State Psychiatric Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The aim of this project is to study the use of gabapentin in reducing benzodiazepine abuse in methadone maintenance patients. A second aim is to study the effects of gabapentin on craving, mood, anxiety, and sleep disturbance in methadone maintenance patients abusing benzodiazepines. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Benzodiazepine Dependence, Opioid Dependence
What is being tested?
Gabapentin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
19 participants
Where
1 siteUnited States
Study dates
Jan 2007to Jan 2011
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men and women between the ages of 18-65 who meet DSM-IV criteria for benzodiazepine abuse or dependence, and opioid dependence, and are being treated for opioid dependence with methadone.
  • Individuals seeking treatment for benzodiazepine abuse or dependence.
  • Individuals capable of giving informed consent and capable of complying with study procedures.
  • Individuals must have current benzodiazepine use.
  • Individuals must report using, benzodiazepines an average > 4 days per week over the past 28 days. The average amount of benzodiazepine used per using day must be > lorazepam 4 mg/day or its equivalent
  • (1 mg lorazepam = 0.25 mg clonazepam = 0.5 mg alprazolam = 5 mg diazepam = 10 mg chlordiazepoxide)
  • Women of child-bearing age will be included provided that they are not pregnant, based on the results of a blood pregnancy test done at the time of screening and agree to use a method of contraception with proven efficacy and not to become pregnant during the study.

Who cannot join

  • Subjects with any current Axis I psychiatric disorder as defined by DSM-IV-TR supported by the SCID-I/P that in the investigator's judgment that are unstable or would be disrupted by study medication or by an effort to discontinue benzodiazepines. Disorders that are stable on psychotherapy or pharmacotherapy will not be exclusionary.
  • Individuals with evidence of acute physiological benzodiazepine withdrawal.
  • Individuals with a history of seizures during alcohol or sedative-hypnotic withdrawal.
  • Individuals with a history of requiring pharmacologic detoxification from alcohol or sedative-hypnotic agents in the past year.
  • Individuals meeting DSM IV criteria for current cocaine dependence as their primary substance use disorder diagnosis.
  • Unstable physical disorders that might make participation hazardous such as uncontrolled hypertension and tachycardia (SBP > 150 mm Hg, DBP > 90 mm Hg, or a sitting quietly HR > 100 bpm), acute hepatitis (patients with chronic mildly elevated transaminase levels [2-3 x upper limit of normal] are acceptable) or poorly controlled diabetes. Kidney disease or impaired kidney function that would interfere with the excretion of gabapentin is exclusionary.
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  • Patients currently taking prescribed psychotropic medications, other than methadone or medications prescribed for pain syndromes, that would be disrupted by study medication or by an effort to discontinue benzodiazepines. Anticonvulsants prescribed for pain syndromes are exclusionary.
  • Patients with a known sensitivity to gabapentin.
  • Individuals who have exhibited suicidal or homicidal behavior within the past two years or have current active suicidal ideation.
  • Women who are pregnant or nursing.
  • Individuals physiologically dependent on any other drugs (excluding nicotine, caffeine, methadone).
  • Individuals currently prescribed gabapentin.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Bridge Plaza Treatment and Rehabilitation Clinic

    Long Island City, New York, 11101

Other trials in United States

About this study

Official title: A Randomized Controlled Pilot Trial of Gabapentin for the Treatment of Benzodiazepine Abuse in Methadone Maintenance Patients

The aim of this project is to study the use of gabapentin in reducing benzodiazepine abuse in methadone maintenance patients. A second aim is to study the effects of gabapentin on craving, mood, anxiety, and sleep disturbance in methadone maintenance patients abusing benzodiazepines. The proposed protocol is a randomized, double-blind, placebo-controlled pilot outpatient trial of gabapentin in the treatment of benzodiazepine abuse in methadone maintenance patients. All subjects will receive weekly manual-guided psychotherapy directed at achieving abstinence and improving current functioning. The primary outcome measure, benzodiazepine use, will be assessed weekly by a combination of self-report (time line follow-back method) and urine toxicology. Associated psychological symptoms of craving, mood, anxiety, and sleep disturbance, will be assessed by a combination of clinician and self-rated instruments.

The investigators hypothesize that individuals receiving methadone maintenance treatment who are abusing (nonprescribed use) benzodiazepines have difficulty in reducing or discontinuing benzodiazepine use because of the significant anxiety, mood, and sleep disturbance symptoms that accompany reduction in use. Gabapentin, an anticonvulsant which has anxiolytic and sedating properties, may alleviate the symptoms associated with a reduction in benzodiazepine abuse and make the achievement of abstinence more likely when administered in the setting of an active psychotherapy condition.

Read the detailed description

The investigators will recruit individuals with current benzodiazepine abuse or dependence, as defined by the DSM-IV, who are receiving methadone maintenance treatment at the Bridge Plaza Treatment and Rehabilitation Clinic. The initial step in recruitment for all patients will be a referral from a clinic counselor.

The investigators plan to enroll 86 participants into the study. Both males and females will be recruited. The distribution of benzodiazepine abuse in methadone maintenance populations with regard to race and gender is not well studied.The investigators expect the gender and racial distribution of subjects to reflect the demographic nature of the Bridge Plaza Treatment and Rehabilitation Clinic; which is approximately 33% Caucasian, 33% African-American, and 33% Hispanic; and 40% female. The investigators will make every effort to recruit minority patients in order to ensure the ability to generalize our findings to the overall treatment population.

All patients will begin medication at the start of the study. Subjects will take medication twice each day, once in the morning and once in the evening. All tablets (placebo and study medication) will be over-capsulated with riboflavin to measure compliance. The placebo group will have a dosing schedule that is identical to the gabapentin group (i.e., they will take the same number of pills each day). Medication will be dispensed weekly in individual vials identified by patient, with dosing instructions written on the outside of the vials. Patients in the placebo group will not receive gabapentin at any time during the study. Gabapentin will be administered in 400 mg tablets; placebo tablets will appear identical to the gabapentin tablets. Gradual increases in medication doses are used in order to minimize side effects and enhance compliance. At the start of week 1, the group receiving gabapentin will be administered at 400 mg three-times a day. This dose will be increased to 800 mg three-times a day at week 2 and increased to 1200 mg three-times a day at the start of week 3. The dose will continue at 1200 mg three-times a day for weeks 3 through 8. Dose reductions for tolerability will be made by the research psychiatrist in coordination with the research pharmacy. All patients must take a minimum of gabapentin/placebo 400 mg BID to remain in the study.

Both the active and placebo medication capsules will contain riboflavin, which will allow the clinic to verify that the study medication is being taken correctly and absorbed by the body. Urine samples obtained weekly will be examined under a UV lamp in order to observe any fluorescence signifying the consumption of the study capsules. The patient will consume approximately 100 mg of riboflavin daily.

The goal of compliance enhancement therapy is to achieve high quality supportive treatment as well as consistency between treatment groups. Treatment will be delivered in 9 individual sessions over 9 weeks. Sessions will last approximately 30 minutes and will be structured, focused on setting abstinence from benzodiazepine use as a goal, patient compliance, and current functioning. The therapist will promote a positive supportive therapeutic relationship with the treatment goal of encouraging abstinence from benzodiazepines and adherence to study visits and medication.

Being tested
Gabapentin, Placebo
Keywords
Benzodiazepine, Gabapentin, Methadone
Medical subject headings
Opioid-Related Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GabapentinDrug

    Also called Neurontin

    For the first week, one 400 mg Gabapentin capsule taken 3 times per day. For the second week, two 400 mg Gabapentin capsules taken 3 times per day. For the third week through the eighth week, three 400 mg Gabapentin capsules taken 3 times per day. For the ninth and last week, two 400 mg Gabapentin capsules taken 3 times per day for 3 days, then one 400 mg Gabapentin capsule taken 3 times per day for 4 days. Placebo study medication appears identical to active medication and is prescribed with an identical dosing schedule.

  • PlaceboDrug

    placebo comparator appears identical to active medication and is prescribed with an identical dosing schedule with a maximum dose of 400mg taken three times per day

Study groups in NCT00420771
Study groupRoleWhat they receive
GabapentinExperimentalgabapentin treatment 1200 mg three times daily
Receives: Drug: Gabapentin
PlaceboPlacebo comparatorPlacebo condition received pills identical in appearance to experimental arm.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Reduction Change in Benzodiazepine Use Per Day Based on Time Line Follow Back

    Comparing the mean reduction change in Benzodiazepine use per day when comparing the baseline week prior to study entry to the last week of study participation based on the Time Line Follow Back

    Measured: data collected during 8 weeks of trial or length of participation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jan 2007 (estimated)
  2. Study startJan 2007
  3. Primary completionJan 2011
  4. Study completionJan 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00420771
Sponsor's protocol ID
4906/#5998R
Other IDs
K23DA021209
Status last verified
Apr 2019
First submitted
8 Jan 2007
Last updated
24 Apr 2019
Data monitoring committee
No
Individual data sharing
No

Publications

  • Mariani JJ, Malcolm RJ, Mamczur AK, Choi JC, Brady R, Nunes E, Levin FR. Pilot trial of gabapentin for the treatment of benzodiazepine abuse or dependence in methadone maintenance patients. Am J Drug Alcohol Abuse. 2016 May;42(3):333-40. doi: 10.3109/00952990.2015.1125493. Epub 2016 Mar 10.

    PubMed 26962719

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