GLP-1R Agonist Treatment for Opioid Use Disorder

NCT ID: NCT06548490

Last Updated: 2025-08-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-13
• Study Completion Date: 2026-11-30

Brief Summary

The goal of this clinical trial is to learn if semaglutide can reduce illicit opioid use in adults in outpatient treatment for opioid use disorder, and who are receiving either buprenorphine or methadone maintenance treatment. The main question it aims to answer is:

• Does semaglutide increase the likelihood that participants will refrain from using illicit and nonprescribed opioids?

The investigators will compare semaglutide to a placebo (a needle prick that contains no drug) to see if semaglutide works to reduce use of illicit and nonprescribed opioids.

The participants will:

• Take semaglutide or a placebo every week for 12 weeks
• Visit the clinic every week for urine drug screening and pregnancy testing, vital signs, and to complete mental health and drug use questionnaires
• Complete smartphone surveys sent at set times during the study

Detailed Description

The purpose of this study is to determine whether 12 weeks of once-weekly treatment with the glucagon-like peptide-1 receptor (GLP-1R) agonist, semaglutide, will reduce illicit opioid use over a 19 week period (129-172 days) among individuals in outpatient treatment for opioid use disorder, and who are receiving either buprenorphine or methadone maintenance treatment (i.e., medication for opioid use disorder; MOUD). Following successful consent and initiation of screening, participants will complete a baseline evaluation and begin a baseline data collection period. If screened into the study, they will be randomly assigned to semaglutide or placebo control arms, in a 1:1 ratio using a permuted-block randomization algorithm stratified by site and MOUD, and begin a 1-week baseline period. Semaglutide (injector pen) or placebo will be administered as a subcutaneously (SC) once per week for 12 weeks, starting at a dose of 0.25 mg SC and advanced on a fixed-flexible dose schedule, based on tolerability, to a dose of 1.0 mg SC per week, or the maximum tolerated dose if less than 1.0 mg. Participants will receive study intervention in an outpatient setting for a total of 12 weeks. After the 12-week intervention, participants will discontinue semaglutide or placebo and be observed for an additional week (wash-out period). A final follow-up visit will then take place approximately 4 weeks after the washout visit (calculated as 18 weeks after Baseline/Treatment Visit 1).

During each study visit, participants will undergo urine drug screening and pregnancy testing, vital signs collection, and complete mental health and drug use questionnaires. Participants will also complete smartphone surveys sent at set times during the study. Blood samples will be collected at 2 of the visits (screening and the study week 14) and a physical examination and medical history collection will be done at the baseline visit.

Conditions

Opioid Use Disorder; Opioid Abuse and Addiction; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorder; Opioid

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Investigational group

Participants randomized to semaglutide will be started at a low dose (0.25 mg once per week) which will be gradually increased weekly until 1.0 mg is reached at Week 4 of the intervention.

Group Type: EXPERIMENTAL

Semaglutide Pen Injector

Intervention Type: DRUG

Semaglutide will be provided using an injection pen

Control group

Participants in the control group will have placebo administered once per week.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be a dry needle stick; no substances will be injected

Interventions

Semaglutide Pen Injector

Semaglutide will be provided using an injection pen

Intervention Type: DRUG

Placebo

Placebo will be a dry needle stick; no substances will be injected

Intervention Type: DRUG

Other Intervention Names

Ozempic; Dry needle stick

Eligibility Criteria

Inclusion Criteria

• Age 18 to 75 years.
• Body mass index (BMI) > 18.
• Able and willing to provide informed consent prior to any study-related activities.
• Current diagnosis of Diagnostic and Statistical Manual Diploma in Social Medicine (DSM)-5 Opioid Use Disorder (OUD) as per the Mini International Neuropsychiatric Interview (MINI) or per the site clinic diagnosis. Patients are eligible if they have a MINI > 3 ("moderate" or "severe" in the "Specify If" box in the Substance Use Disorder (Non-Alcohol) module for the category of opiates).
• Currently receiving outpatient treatment for OUD and at least 2 weeks on buprenorphine (BUP) or 4 weeks on methadone at the study site and/or at an associated clinic at the time of enrollment.
• Have at least 1 urine test positive for opioids after 2 weeks on BUP or 4 weeks on methadone.
• Have positive self-reporting of opioid use after 2 weeks on BUP or 4 weeks on methadone.
• If anatomically capable of becoming pregnant and of childbearing age, is not pregnant (confirmed) or breastfeeding at the time of enrollment and agrees to use a medically accepted method of birth control or to abstain from sexual intercourse while in the study.
• Able to read and communicate in English to the level required to accept standard care and complete all study requirements.
• Able and willing to engage/adhere to the entirety of the study protocol (19 weeks).
• Not currently a prisoner.

Exclusion Criteria

• Age < 18 or > 75 years.
• BMI <18.
• Individuals who are pregnant, planning pregnancy, breastfeeding, or unwilling to use adequate contraceptive measures.
• Current use of glucagon-like peptide 1 receptor (GLP-1R) agonist.
• History of angioedema, serious hypersensitivity reaction, or anaphylactic reaction to semaglutide or another GLP-1R agonist.
• Personal or family history of medullary thyroid carcinoma (MTC) or patients with multiple endocrine neoplasia syndrome Type 2 (MEN 2) or thyroid nodule.
• Type 1 diabetes or history of diabetic ketoacidosis.
• Type 2 diabetes mellitus or current use of a dipeptidyl peptidase-4 (DPP-4) inhibitor.
• Past 30-day use of Sincalide, Sulfonylureas, insulin and insulin products or other medications that may interact with semaglutide.
• Hypoglycemia on intake visit (blood glucose < 60 mg/dL).
• End-stage renal failure, on dialysis, or glomerular filtration rate (GFR) <30 mL/min per 1.73 square meters or previous renal transplant.
• End stage liver disease or previous liver transplant.
• Current or past diagnosis of pancreatitis, gastroparesis, or other severe gastrointestinal (GI) disease.
• Current or past diagnosis of gallbladder disease or gallstones.
• Serious cardiovascular disease within the past 6 months (e.g. uncontrolled hypertension, heart failure, significant cardiac arrhythmias, myocardial infarction, presence of angina pectoris, symptomatic coronary artery disease, deep vein thrombosis, pulmonary embolism, second- or third-degree heart block, mitral valve or aortic stenosis, hypertrophic cardiomyopathy, stroke).
• Severe co-occurring psychiatric disorder (e.g., bipolar disorder, psychotic disorder, schizophrenia), and/or history or evidence of organic brain disease or dementia that would compromise safety or compliance with the study protocol in the opinion of the site principal investigator (PI) and/or physician. As there is no specific scale that determines this, this will include the Site PI/physician determining if the potential participant shows consistency in decision making and if they are alert and oriented to time, date, day and location.
• Significant risk of suicide requiring a different/higher level of care, according to the clinical judgment of the study physician or site principal investigator, or history of suicide attempts within the past 1 year, unless participation is cleared by clinician assessment and/or judgment. A Columbia-Suicide Severity Rating Scale (C-SSRS) indicating a history of suicide attempts within the past year, or active suicidal ideation within the past 1 month, will qualify as significant risk of suicide.
• Treatment with any investigational drug in the one month preceding the study.
• Any contraindication to both methadone and BUP.
• Any contraindication to a GLP-1R agonist.
• Previous randomization for participation in this trial.
• Any other condition at screening that precludes safe participation in the trial in the judgment of the site PI or study physician.
• Plans for travel outside of the local area over the 19 weeks (1 week of baseline, 12 weeks of medication, 1 week wash-out, and follow-up after a further 28 days) that would interfere with visits during the study period or other logistic factors that would make it difficult to commit to the entire duration of study.
• Currently a prisoner.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

New York University

OTHER

Sponsor Role: collaborator

University of Maryland

OTHER

Sponsor Role: collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Milton S. Hershey Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Patricia Sue Grigson

Chairperson (Academic Administrator) Neural and Behavioral Sciences

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jennifer Nyland, PhD

Role: PRINCIPAL_INVESTIGATOR

Milton S. Hershey Medical Center

Locations

University of Maryland Baltimore

Baltimore, Maryland, United States

Site Status: RECRUITING

NYU Langone Health

New York, New York, United States

Site Status: RECRUITING

Pennsylvania Psychiatric Institute

Harrisburg, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jennifer Nyland, PhD

Role: CONTACT

jnyland@pennstatehealth.psu.edu

717-531-6172

Kirsten Shuler, MSc

Role: CONTACT

kshuler@pennstatehealth.psu.edu

717-531-4104

Facility Contacts

Eric Weintraub

Role: primary

eweintra@som.umaryland.edu

Mat Kladney

Role: primary

mathew.kladney@nyulangone.org

929 573 0673

Subi Upadhyay

Role: primary

supadhyay1@pennstatehealth.psu.edu

Angela Spangler

Role: backup

aspangler@pennstatehealth.psu.edu

(717) 683-7838

References

Freet CS, Shuler K, Kawasaki S, Weintraub E, Greenblatt A, Kladney M, Nunes E, Foster KL, Kong L, Raja-Khan N, Cleveland HH, Grigson PS, Bunce SC, Brick TR, Nyland JE. Efficacy of the GLP-1 receptor agonist, semaglutide, in abstinence from illicit and nonprescribed opioids in an outpatient population with treatment-refractory OUD: A randomized, double-blind, placebo-controlled clinical trial protocol. Res Sq [Preprint]. 2025 May 26:rs.3.rs-6666196. doi: 10.21203/rs.3.rs-6666196/v1.

Reference Type: DERIVED

PMID: 40502777 (View on PubMed)

Other Identifiers

UH3DA050325

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00024676

Identifier Type: -

Identifier Source: org_study_id