Clinical trial NCT06548490: GLP-1R Agonist Treatment for Opioid Use Disorder
Official title: GLP-1R Agonist Treatment for Opioid Use Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
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
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: New York University
name: University of Maryland
name: National Institute on Drug Abuse (NIDA)
First posted: 2024-08-12
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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; MOUD). 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 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 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.

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.

Primary outcomes:
measure: Number of participants being abstinent from illicit and nonprescribed opioids.
timeFrame: Study week 2
measure: Number of participants being abstinent from illicit and nonprescribed opioids.
timeFrame: Study week 3
measure: Number of participants being abstinent from illicit and nonprescribed opioids.
timeFrame: Study week 4
measure: Number of participants being abstinent from illicit and nonprescribed opioids.
timeFrame: Study week 5
measure: Number of participants being abstinent from illicit and nonprescribed opioids.
timeFrame: Study week 6
measure: Number of participants being abstinent from illicit and nonprescribed opioids.
timeFrame: Study week 7
measure: Number of participants being abstinent from illicit and nonprescribed opioids.
timeFrame: Study week 8
measure: Number of participants being abstinent from illicit and nonprescribed opioids.
timeFrame: Study week 9
measure: Number of participants being abstinent from illicit and nonprescribed opioids.
timeFrame: Study week 10
measure: Number of participants being abstinent from illicit and nonprescribed opioids.
timeFrame: Study week 11
measure: Number of participants being abstinent from illicit and nonprescribed opioids.
timeFrame: Study week 12
measure: Number of participants being abstinent from illicit and nonprescribed opioids.
timeFrame: Study week 13
Secondary outcomes:
measure: Self-reported opioid craving scores as assessed via smartphone surveys
timeFrame: Study week 1
measure: Self-reported opioid craving scores as assessed via smartphone surveys
timeFrame: Study week 2
measure: Self-reported opioid craving scores as assessed via smartphone surveys
timeFrame: Study week 5
measure: Self-reported opioid craving scores as assessed via smartphone surveys
timeFrame: Study week 9
measure: Self-reported opioid craving scores as assessed via smartphone surveys
timeFrame: Study week 13
measure: Self-reported opioid craving scores as assessed via smartphone surveys
timeFrame: Study week 14
measure: Self-reported opioid craving scores as assessed via smartphone surveys
timeFrame: Study week 18
measure: Self-reported opioid craving as assessed via In-person Cravings Scales scores
timeFrame: Study week 2
measure: Self-reported opioid craving as assessed via In-person Cravings Scales scores
timeFrame: Study week 3
measure: Self-reported opioid craving as assessed via In-person Cravings Scales scores
timeFrame: Study week 4
measure: Self-reported opioid craving as assessed via In-person Cravings Scales scores
timeFrame: Study week 5
measure: Self-reported opioid craving as assessed via In-person Cravings Scales scores
timeFrame: Study week 6
measure: Self-reported opioid craving as assessed via In-person Cravings Scales scores
timeFrame: Study week 7
measure: Self-reported opioid craving as assessed via In-person Cravings Scales scores
timeFrame: Study week 8
measure: Self-reported opioid craving as assessed via In-person Cravings Scales scores
timeFrame: Study week 9
measure: Self-reported opioid craving as assessed via In-person Cravings Scales scores
timeFrame: Study week 10
measure: Self-reported opioid craving as assessed via In-person Cravings Scales scores
timeFrame: Study week 11
measure: Self-reported opioid craving as assessed via In-person Cravings Scales scores
timeFrame: Study week 12
measure: Self-reported opioid craving as assessed via In-person Cravings Scales scores
timeFrame: Study week 13
measure: Number of subjects who sustained abstinence from opioids (Binary indicator)
timeFrame: Study week 10
measure: Number of subjects who sustained abstinence from opioids (Binary indicator)
timeFrame: Study week 11
measure: Number of subjects who sustained abstinence from opioids (Binary indicator)
timeFrame: Study week 12
measure: Number of subjects who sustained abstinence from opioids (Binary indicator)
timeFrame: Study week 13
measure: Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)
timeFrame: Study week 10
measure: Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)
timeFrame: Study week 11
measure: Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)
timeFrame: Study week 12
measure: Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)
timeFrame: Study week 13
measure: Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 2
measure: Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 3
measure: Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 4
measure: Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 5
measure: Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 6
measure: Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 7
measure: Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 8
measure: Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 9
measure: Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 10
measure: Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 11
measure: Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 12
measure: Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 13
measure: Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 2
measure: Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 3
measure: Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 4
measure: Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 5
measure: Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 6
measure: Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 7
measure: Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 8
measure: Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 9
measure: Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 10
measure: Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 11
measure: Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 12
measure: Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
timeFrame: Study week 13
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland Baltimore
state: Maryland
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Harrisburg
country: United States
facility: Pennsylvania Psychiatric Institute
state: Pennsylvania
Study officials:
affiliation: Milton S. Hershey Medical Center
name: Jennifer Nyland, PhD
role: PRINCIPAL_INVESTIGATOR
References: