GLP-1R Agonist Treatment for Opioid Use Disorder

NCT06548490 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY00024676UH3DA050325
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 3

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

Conditions

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

Keywords

Opiate treatment; Opioid treatment; Glucagon-Like Peptide-1 Agonist; Opioid use disorder; Semaglutide

Outcome Measures

Primary Outcomes (12)

• Number of participants being abstinent from illicit and nonprescribed opioids.

  Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.

  Study week 2

• Number of participants being abstinent from illicit and nonprescribed opioids.

  Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.

  Study week 3

• Number of participants being abstinent from illicit and nonprescribed opioids.

  Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.

  Study week 4

• Number of participants being abstinent from illicit and nonprescribed opioids.

  Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.

  Study week 5

• Number of participants being abstinent from illicit and nonprescribed opioids.

  Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.

  Study week 6

• Number of participants being abstinent from illicit and nonprescribed opioids.

  Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.

  Study week 7

• Number of participants being abstinent from illicit and nonprescribed opioids.

  Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.

  Study week 8

• Number of participants being abstinent from illicit and nonprescribed opioids.

  Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.

  Study week 9

• Number of participants being abstinent from illicit and nonprescribed opioids.

  Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.

  Study week 10

• Number of participants being abstinent from illicit and nonprescribed opioids.

  Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.

  Study week 11

• Number of participants being abstinent from illicit and nonprescribed opioids.

  Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.

  Study week 12

• Number of participants being abstinent from illicit and nonprescribed opioids.

  Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.

  Study week 13

Secondary Outcomes (51)

• Self-reported opioid craving scores as assessed via smartphone surveys

  Study week 1

• Self-reported opioid craving scores as assessed via smartphone surveys

  Study week 2

• Self-reported opioid craving scores as assessed via smartphone surveys

  Study week 5

• Self-reported opioid craving scores as assessed via smartphone surveys

  Study week 9

• Self-reported opioid craving scores as assessed via smartphone surveys

  Study week 13

Study Arms (2)

Investigational group

EXPERIMENTAL

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.

Drug: Semaglutide Pen Injector

Control group

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Semaglutide Pen Injector DRUG

Semaglutide will be provided using an injection pen

Also known as: Ozempic

Investigational group

Placebo DRUG

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

Also known as: Dry needle stick

Control group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• New York University: collaborator
• University of Maryland: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (3)

University of Maryland Baltimore

Baltimore, Maryland, 21223, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Pennsylvania Psychiatric Institute

Harrisburg, Pennsylvania, 17110, United States

RECRUITING

Related Publications (2)

• 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 OUD: a randomized, double-blind, placebo-controlled clinical trial protocol. Addict Sci Clin Pract. 2025 Oct 30;20(1):89. doi: 10.1186/s13722-025-00618-2.

  PMID: 41168808 DERIVED

• 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.

  PMID: 40502777 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders; Behavior, Addictive; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Compulsive Behavior; Impulsive Behavior; Behavior

Study Officials

• Jennifer Nyland, PhD

  Milton S. Hershey Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Nyland, PhD

CONTACT

717-531-6172; jnyland@pennstatehealth.psu.edu

Kirsten Shuler, MSc

CONTACT

717-531-4104; kshuler@pennstatehealth.psu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chairperson (Academic Administrator) Neural and Behavioral Sciences

Study Record Dates

• First Submitted: August 7, 2024
• First Posted: August 12, 2024
• Study Start: January 13, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)