Using semaglutide to help reduce opioid use in patients undergoing treatment for opioid use disorder

GLP-1R Agonist Treatment for Opioid Use Disorder

This study is testing if the medication semaglutide can help adults in outpatient treatment for opioid use disorder reduce their use of illicit opioids.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Milton S. Hershey Medical Center (Academic / other)
• Locations: 3 sites (Baltimore, Maryland and 2 other locations)
• Trial ID: NCT06548490 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of semaglutide, a glucagon-like peptide-1 receptor agonist, in reducing illicit opioid use among adults receiving outpatient treatment for opioid use disorder with either buprenorphine or methadone. Participants will be randomly assigned to receive either semaglutide or a placebo for 12 weeks, with weekly clinic visits for monitoring and assessments. The study will measure the likelihood of participants refraining from using illicit opioids through urine drug screenings and self-reported usage. The trial will also include a follow-up period to assess the lasting effects of the treatment.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 75 who are currently diagnosed with opioid use disorder and are receiving outpatient treatment with buprenorphine or methadone.

Not a fit: Patients who are not currently undergoing treatment for opioid use disorder or those who do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for individuals struggling with opioid use disorder, potentially leading to reduced illicit opioid use.

How similar studies have performed: While the use of GLP-1R agonists for opioid use disorder is a novel approach, similar studies targeting substance use disorders have shown promising results.

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.

Where this trial is running

Baltimore, Maryland and 2 other locations

• University of Maryland Baltimore — Baltimore, Maryland, United States (Recruiting)
• NYU Langone Health — New York, New York, United States (Recruiting)
• Pennsylvania Psychiatric Institute — Harrisburg, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Jennifer Nyland, PhD — Milton S. Hershey Medical Center
• Study coordinator: Jennifer Nyland, PhD

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