Exenatide for Treating Cocaine Use Disorder
Condition: Cocaine Use Disorder
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to collect information about whether exenatide (Bydureon) may be
      safe and helpful as a medication treatment for individuals who want to stop using cocaine.

      Although exenatide (Bydureon) is approved by the Food and Drug Administration (FDA) for the
      treatment of type 2 diabetes, it has not been approved by the FDA to treat cocaine use;
      therefore, it is called an investigational drug.
    

Detailed description: 
      Cocaine use continues to be a significant public health problem with limited treatment
      options and no approved pharmacotherapies. Glucagon-like peptide 1 (GLP-1) receptors are
      located in brain areas important for reward and, as such, appear to play a significant role
      in modulating addictive-like behaviors and drug use (Eren-Yazicioglu et al. 2020).
      Extended-release exenatide is a GLP-1 receptor agonist approved by the FDA for the treatment
      of type 2 diabetes. In preclinical studies, exenatide reduces cocaine-seeking and
      cocaine-taking behavior (Brunchmann et al. 2019). The effect of extended-release exenatide on
      cocaine use in patients with a cocaine use disorder (CUD) has not yet been investigated. A
      series of four case studies are being proposed to collect preliminary data on the
      feasibility, safety, and clinical effects of exenatide in treatment-seeking patients with
      CUD.

      The U.S. is facing a re-emergence of cocaine as an epidemic drug, indicated by increases in
      availability, use, and overdose deaths following a previous period of decline (Maxwell 2020).
      Although significant strides have been made in medication development for the treatment of
      cocaine use disorder (CUD), no FDA-approved pharmacotherapies are currently available. NIDA's
      current strategic plan prioritizes efforts to accelerate CUD medication development by
      rigorously testing novel molecular targets based on a translational research approach.
      Emerging evidence supports the potential clinical utility of glucagon-like peptide 1 (GLP-1)
      receptor stimulation for the treatment of substance use disorders, including CUD.

      GLP-1 is an incretin hormone that promotes insulin secretion from pancreatic beta cells.
      Current evidence shows that GLP-1 receptors are widely expressed in areas of the mesolimbic
      dopaminergic pathway where they regulate the rewarding value of food and drugs of abuse,
      including cocaine. Preclinical literature suggests that activation of GLP-1 receptors reduces
      the rewarding effects of cocaine and cocaine self-administration (e.g., Hernandez et al.
      2018; Hernandez et al. 2019). In the human laboratory, acute cocaine administration decreases
      GLP-1 concentrations, with changes associated with subjective reinforcing responses to
      cocaine ("feeling high, anxious") (Bouhlal et al. 2017). Thus, there is compelling evidence
      to hypothesize that exenatide treatment will decrease cocaine use in individuals with CUD. In
      preparation for conducting a full-scale efficacy trial, the goal of the current proposal is
      to collect preliminary feasibility, safety, and clinical data on the effects of exenatide in
      series of four case studies.
    

Intervention name(s): Exenatide 2 mg [Bydureon]; Drug Counseling
Intervention type(s): Drug; Behavioral
Intervention description(s): Exenatide will be purchased commercially as Bydureon® for subcutaneous (SC) injection and administered at a dose of 2 mg once a week for a total of 6 weeks. Each single-dose, dual-chamber pen contains 0.65 mg of diluent and 2 mg of exenatide, which remains isolated until mixed.; Once weekly drug counseling sessions for cocaine use with trained masters-level therapists.
Other intervention name(s): Bydureon
Intervention MeSH terms: Exenatide
Intervention model: Single Group Assignment
Intervention model description: Case series design run as a single-arm open-label pilot
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Cocaine use; Exenatide; Cocaine treatment