Improving Buprenorphine Detoxification Outcomes With Isradipine
Condition: Opioid Dependence
MeSH terms: Opioid-Related Disorders
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This application seeks to address the problem of opioid withdrawal by examining the utility
      of the L-type calcium channel blocker (CCB) isradipine as an adjunct to BUP detoxification.
      This project will address the need for improved detoxification strategies by assessing the
      tolerability and preliminary efficacy of adjunct isradipine during a BUP detoxification in
      opioid-dependent participants. This pilot clinical trial will determine the potential utility
      of the L-type CCB isradipine to improve treatment outcomes in up to 60 opioid-dependent
      individuals undergoing a BUP detoxification procedure. Specifically, this study will
      determine the efficacy of isradipine to reduce withdrawal symptoms, craving, and illicit use
      of opioids in opioid-dependent individuals undergoing BUP detoxification and determine the
      tolerability and safety of controlled-release isradipine (10 mg/day) in opioid-dependent
      individuals undergoing BUP detoxification. Currently, the only FDA-approved medications for
      opioid withdrawal are the opioid agonists methadone and BUP, both of which have abuse
      liability. Our findings, if positive, will support a larger phase II clinical trial.
    

Detailed description: 
      Opioid dependence continues to be a serious public health problem, particularly with the
      dramatic rise in prescription opioid abuse. Traditional methods of detoxification from
      opioids, including tapering off the opioid agonist methadone or buprenorphine (BUP) and
      supportive treatment of symptomatology with the alpha2-adrenergic receptor agonists, are
      limited by the high relapse rate and/or lack of efficacy in relieving subjective symptoms. In
      addition, transitioning individuals from methadone to BUP maintenance has been limited by the
      need to drastically taper the methadone maintenance dose of methadone-maintained individuals
      prior to switching to BUP maintenance, which can precipitate opiate withdrawal and relapse.
      This application takes a novel approach to address the problem of opioid withdrawal by
      examining the utility of the L-type calcium channel blocker (CCB) isradipine as an adjunct to
      BUP detoxification. L-type CCBs have been shown to alleviate opioid withdrawal in
      opioid-treated nonhumans, to be safe and effective in alleviating withdrawal symptoms in
      human detoxification trials, and to have low abuse potential. Moreover, isradipine was the
      most effective of several CCBs tested and was more effective than the alpha2-adrenergic
      agonist clonidine in blocking naloxone-induced behavioral effects without producing
      self-reported effects associated with high potential for abuse. Thus, this project will
      address the need for improved detoxification strategies by assessing the tolerability and
      preliminary efficacy of adjunct isradipine during a BUP detoxification in opioid-dependent
      participants. The aim of this 8-week randomized, placebo-controlled pilot clinical trial is
      to determine the potential utility of the L-type CCB isradipine to improve treatment outcomes
      in up to 60 opioid-dependent individuals undergoing a BUP detoxification procedure. The
      specific aims are to (Aim 1) determine the efficacy of isradipine to reduce withdrawal
      symptoms, craving, and illicit use of opioids in opioid-dependent individuals undergoing BUP
      detoxification and (Aim 2) determine the tolerability and safety of controlled-release
      isradipine (10 mg/day) in opioid-dependent individuals undergoing BUP detoxification.
      Currently, the only FDA-approved medications for opioid withdrawal are the opioid agonists
      methadone and BUP, both of which have abuse liability. Our findings, if positive, will
      support a larger phase II clinical trial. Ultimately, this work could impact the addiction
      field by providing another pharmacological tool that is efficacious for treating opioid
      withdrawal while having minimal abuse liability. This would shift clinical practice,
      establishing an effective adjunct regimen for BUP detoxification as well as having the
      potential to enhance transition to naltrexone therapy.
    

Intervention name(s): Isradipine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Isradipine extended release formulation; Placebo will consist of microcrystalline cellulose.
Other intervention name(s): microcrystalline cellulose
Intervention MeSH terms: Isradipine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: opioid dependence; buprenorphine; isradipine; opioid withdrawal; opioid detoxification