Clinical trial NCT04941521: Exenatide for Treating Cocaine Use Disorder
Official title: Feasibility of Exenatide, a GLP-1R Agonist, for Treating Cocaine Use Disorder: A Case Series Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cocaine Use Disorder
Keywords: Cocaine use
Exenatide
Cocaine treatment
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
First posted: 2021-06-28
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Case series design run as a single-arm open-label pilot
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Feasibility as Assessed by Number of Participants Who Completed Treatment
timeFrame: Week 6
measure: Drug Safety as Assessed by Total Number of Adverse Events Reported During Treatment
timeFrame: From Week 1 to Week 6
measure: Clinical Effect of Exenatide as Assessed by Cocaine Use During Treatment as Indicated by Number of Participants With Cocaine-positive Urine Drug Screen Results
timeFrame: From Week 1 to Week 6
Secondary outcomes:
measure: Feasibility as Assessed by Number of Participants Enrolled
timeFrame: Week 0
measure: Feasibility as Assessed by Number of Study Visits Attended
timeFrame: From Week 1 to Week 6
measure: Feasibility as Assessed by Retention as Indicated by Total Number of Completed Study Visits
timeFrame: From Week 1 to Week 6
measure: Feasibility as Indicated by Overall Acceptability as Reported on the Satisfaction Survey
timeFrame: Week 6
measure: Clinical Effect of Exenatide as Assessed by Number of Participants Who Self-reported Cocaine Use on 50% or More Days of the Week
timeFrame: From Week 1 to Week 6
measure: Clinical Effect of Exenatide as Indicated by Number of Participants Who Reported a Reduction in Craving by Week 6 as Indicated by Cocaine Craving on the Brief Substance Craving Scale
timeFrame: From Week 0 to Week 6
measure: Clinical Effect of Exenatide as Assessed by Number of Participants Who Had a Decrease in Drug Demand by Week 6
timeFrame: From Week 0 to Week 6
measure: Clinical Effect of Exenatide as Assessed by Number of Participants Who Were Below the Clinical Range for Depression by Week 6 as Indicated by the Beck Depression Inventory
timeFrame: Week 6
measure: Clinical Effect of Exenatide as Indicated by Number of Participants Who Had an Increase in Positive Affect Symptoms by Week 6 as Indicated on the Positive/Negative Affect Schedule
timeFrame: From Week 0 to Week 6
measure: Clinical Effect of Exenatide as Indicated by Number of Participants Who Had a Decrease in Negative Affect Symptoms Indicated on the Positive/Negative Affect Schedule
timeFrame: From Week 0 to Week 6
Other outcomes:
Locations:
city: Houston
country: United States
facility: UTHealth Behavioral and Biomedical Sciences Building
state: Texas
Study officials:
affiliation: UT Houston
name: Joy Schmitz, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UT Houston
name: Luba Yammine, PhD
role: PRINCIPAL_INVESTIGATOR
References: