Evaluation Of Semaglutide in Adults With Cocaine Use Disorder With and Without HIV (STAC)

Evaluation Of Semaglutide Safety and Tolerability in Adults With Cocaine Use Disorder With and Without HIV

The purpose of this research study is to find out if semaglutide is safe and well tolerated in adults with cocaine use disorder who do and do not have human immunodeficiency virus (HIV). Participants will complete a screening process and if you are able to participate, you will be assigned to one of two treatment groups: semaglutide or placebo.

Participants will:

• Visit the clinic once a week for semaglutide or placebo injections
• Visit the clinic once every two weeks for labwork, assessments and/or surveys
• If consented to optional MRI's, complete two MRI's

Study Overview

• Status: Recruiting
• Conditions: HIV; Cocaine Use Disorder
• Intervention / Treatment: Drug: Semaglutide; Drug: Placebo

Detailed Description

STAC is a 16-week, double-blind, placebo-controlled, pilot, dose-escalation study that aims to determine the dose of semaglutide that is safe and tolerable in individuals with cocaine use disorder, including those with and without HIV; whether semaglutide improves drug use outcomes for cocaine use; and whether semaglutide improves cardiac and inflammatory biomarkers. Interested participants will be consented and screened, and after screening process is completed, all eligible participants who desire to continue with the study will be randomized either to semaglutide injections or placebo injections. Participants will receive semaglutide or placebo injections once a week from Day 0 through Week 16, and a final assessment will be completed at Week 16. Study visits will also intermittently complete labwork, medical examinations, clinical assessments and surveys.

Participants who consent to the optional MRI visits, will also complete MRI's at two timepoints: once before starting the study medication and once near Week 16.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Onyinyechi Ogbumbadiugha-Weekes; Phone Number: 443-635-4943; Email: oogbumbadiugha@ihv.umaryland.edu
• Study Contact Backup: Name: Sarah Kattakuzhy; Phone Number: 443-691-4638; Email: skattakuzhy@ihv.umaryland.edu

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20002
      • Recruiting
      • Institute of Human Virology at the University of Maryland School of Medicine
      • Contact: Emade Ebah; Phone Number: 240-667-6202; Email: eebah@ihv.umaryland.edu
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • Institute of Human Virology at the University of Maryland School of Medicine
      • Contact: Onyinyechi Ogbumbadiugha-Weekes; Phone Number: 443-635-4943; Email: oogbumbadiugha@ihv.umaryland.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. At least 18 years old
2. Meet criteria for CUD according to the Diagnostic and Statistical Manual Version 5
3. Used cocaine at least 7 out of the past 14 days
4. Body Mass Index between 20 - 50 kg/m2
5. English proficiency
6. In people of childbearing potential, agree to use an acceptable method of birth control

Exclusion Criteria:

1. Triglycerides > 500 mg/dL
2. History of gall bladder disease
3. Personal or family history of medullary thyroid carcinoma, or patients with a history of Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
4. History of diabetic retinopathy
5. Being prescribed glucose-lowering medications
6. An estimated glomerular filtration rate of less than 45 ml/min
7. Lifetime history of taking semaglutide or other GLP-1 RAs
8. Current suicidal ideation or suicide attempts within the past 24 months
9. Present diagnosis of diabetes mellitus OR screening hemoglobin A1C >/= 6.5
10. Use of weight-lowering medications
11. History of gastric bypass surgery
12. History of myocardial infarction or stroke within the past 12 months
13. Pregnant, breastfeeding, or the patient intends to become pregnant during the next four months
14. Any contraindicated medical issues identified by the study investigators
15. Risk of conditions that are under Warning and Precautions section of OZEMPIC and WEGOVY including but not limited to known history or current report of clinically relevant hypoglycemia, gastroparesis, or pancreatic disease.
16. Calcitonin value equal to or above 50 ng/L
17. If completing the MRI portion of the study: claustrophobia or physical issues preventing MRI scan
18. If completing the MRI portion of the study: presence of a metal device in the body (e.g. pacemaker. Infusion pump, aneurysm clip, metal prosthesis or plate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide; Once weekly injection of semaglutide	Drug: Semaglutide; The initial dose will be semaglutide 0.25mg which, if tolerated, will be escalated to 0.5mg. Escalation will continue to 1.0 mg and afterwards to 2.0 mg. The highest possible dose will be 2.0mg semaglutide.; Other Names: Ozempic; Wegovy
Placebo Comparator: Placebo; Once weekly injection of placebo	Drug: Placebo; Patients randomized to placebo arm will receive placebo injection every week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of semaglutide in patients with cocaine use disorder (CUD) with and without HIV	Number of Grade 3 and 4 adverse effects reported by patients at any time after Day 0	16 weeks
Tolerability of semaglutide in patients with cocaine use disorder (CUD) with and without HIV	Dose of semaglutide the patient tolerates regardless of the presence of adverse effects	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine if semaglutide improves cocaine use frequency in people with CUD with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in cocaine use frequency via timeline followback method. The higher the frequency of cocaine use, the worse the outcome.	16 weeks
Determine if semaglutide reduces cocaine use in people with CUD with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose of mean dollar-amount patients spent on cocaine during the past 7 days. The higher the amount, the worse the outcome.	16 weeks
Determine if semaglutide reduces cocaine use in people with CUD with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in presence of cocaine metabolite detected on urine drug-screen results.	16 weeks
Determine if semaglutide reduces cocaine craving for people with CUD with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in score on Cocaine Craving Questionnaire Brief (CCQ-Brief). Minimum score= 8 (minimal craving). Maximum score= 56 (extreme craving). The higher the score, the worse the outcome.	16 weeks
Determine if semaglutide reduces drug use severity for people with CUD with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in score on the Drug Abuse Screening Test (DAST). Minimum Value= 0 (No problems with drug abuse or dependence. Maximum Value= 10 ( severe drug-related problems). The higher the score, the worse the outcome.	16 weeks
Determine if semaglutide reduces risk taking behavior in people with cocaine use disorder, with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in score on Balloon Analogue Risk Task (BART). Minimum score= 0 (no risk taking). Maximum: Variable, it can go up to 500-1000. Higher Scores= Higher risk taking behavior.	16 weeks
Determine if semaglutide reduces impulsiveness in people with cocaine use disorder, with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in score on Barratt Impulsiveness Scale (BAS-11) Minimum score: 30, Maximum score: 120. Higher score equals high impulsivity.	16 weeks
Determine if semaglutide reduces compulsivity in people with cocaine use disorder, with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in score on Obsessive-Compulsive Cocaine Use Scale. Minimum score: 0 (no symptoms), Maximum Score: 32. Higher score = greater severity of obsessive-compulsive symptoms related to cocaine use. The higher the score, the worse the outcome.	16 weeks
Determine if semaglutide impacts depression in people with cocaine use disorder, with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in score on Patient Health Questionnaire-9 (PHQ-9). Minimum score: 0 (no depressive symptoms). Maximum score: 27 (severe depression). Higher score indicates worse outcome.	16 weeks
Determine if semaglutide impacts anxiety in people with cocaine use disorder, with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in score on Generalized Anxiety Disorder-7 (GAD-7). Minimum score= 0 (no anxiety symptoms). Maximum= 21 (severe anxiety) Higher score indicates worse outcome.	16 weeks
Determine if semaglutide impacts anhedonia in people with cocaine use disorder, with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in score on Snaith-Hamilton Pleasure Scale (SHAPS). Minimum score=0 (no anhedonia). Maximum score=14 (severe anhedonia). The higher the score, the worse the outcome	16 weeks
Determine if semaglutide impacts sleep in people with cocaine use disorder, with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in score on Pittsburgh Sleep Quality Index (PSQI). Minimum score= 0 (good sleep quality). Maximum= 21 (poor sleep quality). The higher the score, the worse the outcome.	16 weeks
Determine if semaglutide impacts sexual desire in people with cocaine use disorder, with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in score on the Sexual Desire Inventory (SDI).- Minimum score= 0 (no sexual desire). Maximum score= 60 (high sexual desire). The lower the score, the worse the outcome.	16 weeks
Determine if semaglutide impacts food cravings in people with cocaine use disorder, with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in score on the General Trait Food Cravings Questionnaire (G-FCQ-T). Minimum score = 0 (no food cravings). Maximum score =7 (high frequency and intensity of cravings). The lower the score, the worse the outcome.	16 weeks
Determine if semaglutide changes levels of inflammatory biomarkers in patients with HIV relative to those without HIV	Levels of HIV-induced inflammation markers (inflammatory cytokines, IFN-g, TNF, IL-6, IL-8, chemokine, IL18, CD163, Neopterin, beta 2 microglobulin, LPS, sCD14, sCD25, IL12, IL10) before and after s.c. semaglutide	16 weeks
Determine if semaglutide changes levels of clinically relevant cardiovascular biomarkers in patients with HIV relative to those without HIV	Levels of cardiovascular biomarkers (levels of high-sensitivity C-reactive protein (CRP), high-sensitivity troponin (hs- hs-TRP), endothelin-1 (ET-1), D-dimer before and after s.c. semaglutide	16 weeks
Determine if semaglutide effects changes in body fat in individuals with cocaine use disorder, with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in percent body fat using the InBody scan. The lower the percent body fat, the worse the outcome.	16 weeks
Determine if semaglutide effects body fat distribution in people with CUD with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in body fat distribution. The more central the body fat distribution, the worse outcomes.	16 weeks
Determine if semaglutide effects changes muscle mass in patients with cocaine use disorder, with and without HIV	Change from baseline to highest tolerated semaglutide or placebo dose in percent muscle mass using the InBody Scan. The lower the percentage of muscle mass, the worse the outcome.	16 weeks
Determine if s.c. semaglutide produces changes in brain function in patients with cocaine use disorder, with and without HIV	Magnetic Resonance Spectroscopy (MRS)will be used to assess whether s.c. semaglutide produces changes in brain metabolite levels; Resting state functional connectivity (RSFC) will be used to assess whether s.c. semaglutide produces changes in brain network function; An Arterial Spin Labeling (ASL) sequence that measures Blood Brain Barrier (BBB) permeability will be used to assess whether s.c. semaglutide produces changes in BBB integrity	16 weeks

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: November 6, 2024
• First Submitted That Met QC Criteria: November 13, 2024
• First Posted (Actual): November 15, 2024

Study Record Updates

• Last Update Posted (Actual): August 24, 2025
• Last Update Submitted That Met QC Criteria: August 18, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: GLP-1; semaglutide; cocaine use disorder
• Additional Relevant MeSH Terms: Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Semaglutide
• Other Study ID Numbers: HP-00112237; 75N90024C00036 (Other Identifier: NIH Clinical Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All de-identified IPD necessary to verify study results
• IPD Sharing Time Frame: IPD and supporting information will be available after study completion.
• IPD Sharing Access Criteria: Investigators can email the Principal Investigator (PI) with access requests and the PI will judge if the use of data is justified. If the PI deems the research question appropriate, the PI will grant access.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes