A Novel Anti-Obesity Drug Combination as a Pharmacotherapy for Cocaine Dependence
Condition: Cocaine Use Disorders
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The research proposed in this application will determine the initial efficacy, safety and
      tolerability of a novel drug combination, bupropion and naltrexone, as a pharmacotherapy for
      cocaine dependence. A rigorous, inpatient human laboratory study will be conducted. The
      proposed study is innovative and important because it will provide the impetus for the
      conduct of double blind, placebo-controlled trials to further demonstrate the efficacy of
      bupropion-naltrexone combinations for managing cocaine dependence.
    

Detailed description: 
      Cocaine (COC) dependence is a significant public health concern. A widely effective
      pharmacotherapy has not yet been identified for COC dependence. Innovative strategies are
      needed to identify an effective pharmacotherapy for COC dependence. Testing medications
      effective for disorders that share neurobiological substrates with drug dependence, for
      example, could yield treatments for managing COC dependence.

      Obesity is also a significant public health concern. Although obesity and COC dependence are
      typically considered distinct clinical entities, both diseases involve perturbations of
      central biogenic amine and/or hypothalamic-melanocortin systems. The obesity epidemic has
      spurred development of medications to promote weight loss. A combination of bupropion (BUP)
      and naltrexone (NTX) is effective for obesity. The overarching goal of this application is to
      demonstrate the initial efficacy, safety, and tolerability of BUP-NTX combinations for COC
      dependence. A mixed-model experiment will be conducted in which separate cohorts of
      non-treatment-seeking, COC-dependent participants will be randomized to different maintenance
      doses of NTX (i.e., NTX is a between-subject factor). Participants (N=12) in each NTX cohort
      will be maintained concurrently on BUP (i.e., BUP is a within-subject factor). The
      reinforcing effects of intranasal COC will be determined after participants in each NTX
      cohort are maintained for 4-7 days on each of the BUP doses (i.e., COC is a within-subject
      factor). COC (0, 40 and 80 mg) will be tested with multiple dose combinations of BUP (0, 100,
      200, 400 mg/day) and NTX (0, 25, 50 mg/day). The proposed study will also identify the
      optimal dose combination of BUP and NTX that most effectively attenuates the reinforcing
      effects of COC.

      This research will provide critical information regarding the initial efficacy and optimal
      doses of a novel drug combination, BUP and NTX, for COC dependence, which will enhance the
      probability of success when advanced to a clinical trial. Innovations of the proposed
      research include: 1) testing a combination of marketed drugs that demonstrated modest
      efficacy when tested as mono-therapies; 2) the use of a sophisticated drug
      self-administration procedure; 3) providing the impetus for the conduct of a Phase II
      clinical trial to further demonstrate the efficacy of BUP-NTX combinations for COC
      dependence; and 4) demonstrating the initial efficacy and optimal doses of a combination of
      commercially available drugs, as opposed to waiting for novel molecules to be available for
      testing in humans, thereby impacting clinical research and practice more quickly. In these
      ways, the proposed project will shift the current clinical research paradigm in
      pharmacotherapy development and have a significant impact on the treatment of COC dependence.
    

Intervention name(s): Bupropion
Intervention type(s): Drug
Intervention description(s): Subjects will be maintained on oral bupropion or placebo during the study.
Intervention MeSH terms: Bupropion
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Basic Science