Exenatide for Treating Cocaine Use Disorder

NCT ID: NCT04941521

Last Updated: 2022-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-24
• Study Completion Date: 2021-11-17

Brief 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.

Conditions

Cocaine Use Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Exenatide and Drug Counseling

Participants will receive once weekly exenatide injections and drug counseling sessions.

Group Type: EXPERIMENTAL

Exenatide 2 mg [Bydureon]

Intervention Type: DRUG

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.

Drug Counseling

Intervention Type: BEHAVIORAL

Once weekly drug counseling sessions for cocaine use with trained masters-level therapists.

Interventions

Exenatide 2 mg [Bydureon]

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.

Intervention Type: DRUG

Drug Counseling

Once weekly drug counseling sessions for cocaine use with trained masters-level therapists.

Intervention Type: BEHAVIORAL

Other Intervention Names

Bydureon

Eligibility Criteria

Inclusion Criteria

• between 18 and 60 years of age.
• meet DSM-5 criteria for current cocaine use disorder as measured by the Structured Clinical Interview for DSM-5 (SCID).
• have at least 1 cocaine-positive urine specimen (≥ 150 ng/mL) during intake.
• be in acceptable health on the basis of interview, medical history and physical exam.
• have hematology and chemistry laboratory tests that are within reference limits (±10%), with the following exception: pancreatic tests (lipase and amylase) must be within normal limits.
• consent to use an acceptable method of birth control during study participation and for one month after discontinuation of the study medication. Non-hormonal methods of contraception are recommended, including barrier contraceptives (e.g., diaphragm, cervical cap, male condom) or intrauterine device (IUD). Steroid contraceptives if used with non-hormonal methods are acceptable.
• be able to understand the consent form and provide written informed consent.
• be able to provide the names of at least 2 persons who can generally locate their whereabouts.

Exclusion Criteria

• current DSM-5 diagnosis for substance use disorder (of at least moderate severity) other than cocaine, marijuana, alcohol, or nicotine.
• current alcohol use that meets for physiological dependence requiring detoxification or makes participation medically unsafe as determined by the medical director.
• have a DSM-5 axis I psychiatric disorder, or anorexia nervosa, or neurological disease or disorder requiring ongoing treatment and/or making study participation unsafe (e.g., psychosis, dementia).
• significant current suicidal or homicidal ideation.
• Type 1 or type 2 diabetes mellitus (previously diagnosed or indicated by HbA1C level of ≥6.5%).
• have medical conditions contraindicating exenatide pharmacotherapy (e.g., personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, severe gastrointestinal disease (severe gastroparesis), previous history of pancreatitis or risk of pancreatitis, creatinine clearance <45 or end stage renal disease, previous medically adverse reaction to exenatide or other GLP-1 receptor agonists).
• taking medications that could adversely interact with exenatide (e.g., oral or injectable blood glucose lowering medications).
• having conditions of probation or parole requiring reports of drug use to officers of the court.
• impending incarceration.
• pregnant or nursing for female patients.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Joy Schmitz

Professor, Faillace Chair, and Director for the Center for Neurobehavioral Research on Addiction

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joy Schmitz, PhD

Role: PRINCIPAL_INVESTIGATOR

UT Houston

Luba Yammine, PhD

Role: PRINCIPAL_INVESTIGATOR

UT Houston

Locations

UTHealth Behavioral and Biomedical Sciences Building

Houston, Texas, United States

Countries

United States

References

Yammine L, Balderas JC, Weaver MF, Schmitz JM. Feasibility of Exenatide, a GLP-1R Agonist, for Treating Cocaine Use Disorder: A Case Series Study. J Addict Med. 2023 Jul-Aug 01;17(4):481-484. doi: 10.1097/ADM.0000000000001147. Epub 2023 Feb 17.

Reference Type: DERIVED

PMID: 37579116 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HSC-MS-21-0241

Identifier Type: -

Identifier Source: org_study_id