GLP-1R Agonist Treatment for Opioid Use Disorder

Phase 2

Not yet recruiting

• Conditions: Opioid Abuse and Addiction; Narcotic-Related Disorders; Chemically-Induced Disorders; Opioid Use Disorder; Substance-Related Disorders; Mental Disorder; Opioid
• Interventions: Drug: Semaglutide Pen Injector; Drug: Placebo

• Registration Number: NCT06548490
• Lead Sponsor: Milton S. Hershey Medical Center

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 (133 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). Following successful consent and screening, participants will complete a baseline evaluation and be randomly assigned to semaglutide or placebo control arms, in a 1:1 ratio using a permuted-block randomization algorithm stratified by site and), 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 target 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 4 weeks at the target (1.0 mg) or maximum the highest dose tolerated dose, 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 5 weeks after the last treatment visit.

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

Study Timeline

• Study First Submitted: 2024-08-07
• Study First Submitted QC: 2024-08-07
• Study First Posted: 2024-08-12
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-18
• Last Update Posted: 2024-12-20
• Study Start: 2025-01
• Primary Completion: 2026-11
• Study Completion: 2026-11

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 200

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.
• 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.
• 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 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.

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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.
• 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.
• Treatment with any investigational drug in the one month preceding the study.
• Any contraindication to methadone, BUP, or 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Investigational group	Semaglutide Pen Injector	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.
Control group	Placebo	Participants in the control group will have placebo administered once per week.

Primary Outcome Measures

Name	Time	Method
Number of participants being abstinent from illicit and nonprescribed opioids.	Study week 13	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)

Secondary Outcome Measures

Name	Time	Method
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire	Study week 13	Validated daily binary indicator for measuring use of stimulants
Self-reported opioid craving as assessed via In-person Cravings Scales scores	Study week 13	Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Self-reported opioid craving scores as assessed via smartphone surveys	Study week 18	Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Number of subjects who sustained abstinence from opioids (Binary indicator)	Study week 13	Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.
Days using opioids over the 12-week treatment period by Timeline Followback questionnaire	Study week 13	Validated daily binary indicator for measuring use of opioids
Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)	Study week 13	Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.

Trial Locations

Locations (1)

Pennsylvania Psychiatric Institute; 🇺🇸 Harrisburg, Pennsylvania, United States