Improving Treatment Outcomes for Prescription Opioid Dependence
Condition: Drug Dependence
MeSH terms: Opioid-Related Disorders; Substance-Related Disorders
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Overall, this proposal seeks to improve treatment strategies for the significant public
      health problem of prescription opioid dependence by determining whether gabapentin, a
      non-narcotic pharmaceutical agent with minimal abuse potential and preliminary efficacy, will
      be effective in ameliorating withdrawal symptoms, craving and illicit drug use in
      prescription opioid dependent participants undergoing a 10-day detoxification from
      buprenorphine. In addition, the acceptability and feasibility of transitioning to depot
      naltrexone therapy will also be determined. If successful, this study would provide data to
      support further development of gabapentin as a pharmacological tool for improved outcomes
      during opioid detoxification as well as an integrated outpatient approach for treating
      prescription opioid dependence.
    

Detailed description: 
      Opioid dependence is a serious public health problem, particularly with the dramatic rise in
      prescription opioid abuse, but long-term opioid agonist maintenance with methadone or
      buprenorphine (BUP) may not be optimal for many prescription opioid abusers. Yet current
      opioid detoxification strategies are limited by high relapse rates and/or lack of efficacy in
      relieving subjective symptoms. In addition, antagonist maintenance with naltrexone (NTX),
      which may be an optimal longer-term strategy for this population, requires prior opioid
      detoxification and has been associated with relatively poor outcomes in heroin abusers. This
      application takes a novel, broad approach to address the problem of prescription opioid
      dependence by determining the 1) utility of adjunct gabapentin (GBP) during outpatient BUP
      detoxification to improve initial outcomes and 2) feasibility of transitioning prescription
      opioid -dependent patients to depot NTX following detoxification, which may improve
      longer-term outcomes. GBP, an N-type calcium channel blocker with low abuse potential,
      potentiates opioid analgesia, decreases both postoperative morphine consumption and
      movement-related pain, and reverses tolerance to the antinociceptive effects of morphine. GBP
      is also well tolerated and effective in reducing craving and illicit opioid use in pilot
      detoxification trials. The efficacy and tolerability of adjunct GBP during BUP-assisted
      detoxification and the feasibility of subsequent transition to depot NTX therapy in
      prescription opioid -dependent participants will be assessed. This 12-week, randomized,
      placebo-controlled clinical trial will determine the potential utility of adjunct GBP in 150
      prescription opioid -dependent individuals undergoing outpatient BUP detoxification and
      whether transition to short-term depot NTX therapy is feasible. Our three specific aims are
      to determine (1) the efficacy and tolerability of GBP to reduce craving and illicit use of
      opioids in prescription opioid-dependent individuals undergoing outpatient BUP
      detoxification; (2) acceptability and feasibility of transition to, and short-term
      maintenance on, depot NTX following detoxification; and (3) prognosticators of completion of
      the BUP taper, successful induction onto depot NTX, symptomatology, and longer-term outcomes.
      Currently, the only Food and Drug Administration (FDA)-approved medications for the treatment
      of opioid withdrawal are the opioid agonists methadone and BUP, both of which have abuse
      liability, and NTX, which can produce low levels of withdrawal-like symptoms, especially
      early in treatment. Findings, if positive, will support further development of GBP as an
      adjunct medication as well as provide an integrated, seamless approach to outpatient
      prescription opioid-dependence treatment. Ultimately, this work could impact the addiction
      field by providing both procedural and pharmacological tools for treating prescription opioid
      dependence that significantly improve outpatient detoxification outcomes and markedly enhance
      access and transition to NTX therapy. This would shift clinical practice, establishing an
      effective adjunct regimen for BUP detoxification and an integrated approach for transition to
      NTX therapy. GBP may also be clinically useful for other situations where opioid withdrawal
      is a concern.
    

Intervention name(s): Gabapentin; Buprenorphine; Clonidine; Naltrexone (oral); Naltrexone (depot); Placebo
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): N-type calcium channel blocker being examined for its potential efficacy to alleviate opioid withdrawal during buprenorphine-assisted detoxification and transition to depot naltrexone.; All participants are stabilized on buprenorphine and then undergo a 10 day taper off buprenorphine.; All participants who successfully taper off buprenorphine receive Clonidine (0.1 mg) prior to induction onto oral naltrexone.; All participants receive increasing doses of oral naltrexone over a 3 day period (day 1: 6.25 and 6.25 mg; day 2: 25 mg; day 3: 50 mg); All participants who tolerate oral naltrexone at 50 mg will receive the naltrexone injection on either the same day as the 50 mg dose or the day after.; Microcrystalline cellulose
Intervention MeSH terms: Clonidine; Naltrexone; Buprenorphine; Gabapentin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment