Semaglutide plus cognitive behavioral therapy for cocaine use disorder

Repurposing Semaglutide for the Treatment of Cocaine Use Disorder: a Pilot Mechanistic Study

This trial will test whether adding semaglutide (a GLP-1 medication) to cognitive behavioral therapy helps adults with cocaine use disorder reduce craving and use.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 75 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The University of Texas Health Science Center, Houston (Academic / other)
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT07227948 on ClinicalTrials.gov

What this trial studies

This Phase 2, randomized, placebo-controlled trial gives participants either semaglutide or placebo alongside standardized cognitive behavioral therapy (CBT) to test whether semaglutide improves outcomes for cocaine use disorder. Eligible participants must meet DSM-5 criteria for CUD, report recent cocaine use confirmed by urine testing, and have a BMI of 25 kg/m2 or higher. Semaglutide is a GLP-1 receptor agonist used for diabetes and obesity, and preclinical studies suggest GLP-1RAs can reduce drug reward and cue-driven responding. The trial is a proof-of-concept effort supported by the NIH HEAL initiative and conducted at The University of Texas Health Science Center at Houston with NIDA collaboration.

Who should consider this trial

Good fit: Adults who meet DSM-5 criteria for cocaine use disorder, have recent cocaine use verified by urine test, have BMI ≥25 kg/m2, agree to CBT, and can attend the Houston site are ideal candidates.

Not a fit: People with BMI below 25, those who are pregnant or unwilling to use required contraception, those without recent cocaine use, or those unable to attend in-person visits are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this approach could reduce cocaine craving and use and make behavioral therapy more effective for people with cocaine use disorder.

How similar studies have performed: Animal studies show GLP-1 receptor agonists can reduce the rewarding effects of cocaine, but human evidence for treating addiction is limited and this is a proof-of-concept trial.

Eligibility criteria

Inclusion Criteria:

* Ability to provide informed consent before any study-related activity, willing to comply with all study procedures, and be available for the duration of the study.
* Meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM 5) diagnostic criteria for CUD and report recent cocaine use (verified by at least one positive urine drug screen (UDS) for the cocaine metabolite benzoylecgonine (BE), during intake).
* Have body mass index (BMI) of ≥25 kg/m2
* Agree (if the participant is female and of child-bearing potential) to use effective contraceptive methods, unless the participant's male partner(s) is surgically sterile (underwent vasectomy). Acceptable contraceptives include oral contraceptives, contraceptive sponge, patch, double barrier (diaphragm/spermicidal or condom/spermicidal), intrauterine contraceptive system, etonogestrel implant, medroxyprogesterone acetate contraceptive injection, complete abstinence from sexual intercourse, and/or hormonal vaginal ring. Contraceptive measures sold for emergency use after unprotected sex are not acceptable methods for routine use. Women of child-bearing potential must provide negative urine pregnancy test prior to randomization. Note: A woman is considered fertile (of childbearing potential) following menarche and until becoming postmenopausal unless permanently sterile. Women in the following categories are not considered a woman of childbearing potential: premenarcheal, premenopausal female with one of the following: documented hysterectomy, documented bilateral salpingectomy, documented bilateral oophorectomy. Postmenopausal female is defined as no menses for 12 months without an alternative medical cause. Females on HRT and whose menopausal status is in doubt will be required to use one of the nonhormonal highly effective contraception methods if they wish to continue their hormone replacement therapy (HRT) during the trial.
* Have a medical and psychiatric history and a brief physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the Study Physician and the Principal Investigator.
* Be able to provide the names of at least 2 persons who can consistently locate their whereabouts.

Exclusion Criteria:

Medical Exclusions

* Personal or first-degree relative(s) history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).
* History or presence of chronic pancreatitis or recent acute pancreatitis.
* Type 1 or type 2 diabetes mellitus (previously diagnosed or indicated by HbA1C ≥48 mol/mol (6.5%) as measured at screening).
* Severe gastrointestinal disease (i.e., severe gastroparesis).
* History of malignant neoplasms within the past 5 years prior to screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed.
* History of severe cardiovascular disease.
* History of retinopathy.
* Systolic blood pressure (SBP) \>180 mmHg and/or diastolic blood pressure (DBP) \>105 mmHg)
* End stage renal disease (ESRD, previously diagnosed or indicated by estimated glomerular filtration rate (eGFR) value of eGFR \< 15 ml/min/1.73 m2 at screening).
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 times the upper limit of normal range at screening.
* Known or suspected hypersensitivity to semaglutide, excipients, or related products.
* History of seizure or elevated risk of seizure.
* Women who are currently pregnant, or plan to become pregnant, or lactating, or of childbearing potential and are not using medically accepted forms of contraception
* Have any medical illness or condition which in the opinion of the PI and/or the Study Physician would preclude safe and/or successful completion of the study.
* Any foreseeable procedure requiring general anesthesia or deep sedation.

Psychiatric/Substance Use Exclusions

* Current ≥ moderate substance use disorder aside from alcohol, nicotine, or marijuana, or a Substance Use Disorder (SUD) requiring medical detoxification (e.g., alcohol, opioid, benzodiazepine)
* Current or recent suicidal ideation.
* Homicidal ideation that requires immediate attention.
* Have any psychiatric illness or condition which in the opinion of the PI and/or the Study Physician would preclude safe and/or successful completion of the study.

Weight-Related Exclusions

* Gained/lost ≥4.5 kg (10 lb.) over the past 6 months (prior to screening).
* Uncontrolled thyroid disease at screening

Medication-Related Exclusions

* Currently using sincalide, sulfonylureas, insulin and insulin products, or medication used for weight management (i.e., orlistat, naltrexone-bupropion, liraglutide, semaglutide, tirzepatide, phentermine, topiramate, benzphetamine, diethylpropion, phendimetrazine).
* Any otherwise not specified concomitant medication that could compromise participant safety or treatment in the opinion of the Study Physician and/or the PIs.

General Exclusions

* Current, anticipated, or pending enrollment in another addiction treatment program and/or research study that could potentially affect participant safety and/or the study data/design as determined by the Principal Investigator and/or Study Physician.
* Not planning to live in the area for the duration of the trial.
* Surgery scheduled for the duration of the trial, except for minor surgical procedures, in the opinion of the PI and/or the Study Physician.
* Unable to communicate (read, write, and speak) fluently in English.

Where this trial is running

Houston, Texas

• The University of Texas Health Science Center at Houston — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Luba Yammine, PhD — The University of Texas Health Science Center, Houston
• Study coordinator: Luba Yammine, PhD

Conditions Cocaine Use Disorder; semaglutide; GLP-1 agonist; cocaine addiction