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NCT Number: NCT06548490

GLP-1R Agonist Treatment for Opioid Use Disorder

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

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Key information

Conditions

Opioid Use Disorder Behavior Behavior, Addictive Chemically-Induced Disorders Compulsive Behavior Impulsive Behavior Mental Disorder Mental Disorders Narcotic-Related Disorders Opioid Opioid Abuse and Addiction Opioid-Related Disorders Substance-Related Disorders

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Maryland Baltimore, Baltimore, Maryland, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 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 or to abstain from sexual activity that could result in pregnancy (if applicable) 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.

Treatment and study plan

Semaglutide Pen Injector

Drug

Semaglutide will be provided using an injection pen

Other names: Ozempic

Placebo

Drug

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

Other names: Dry needle stick

Primary outcomes

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

    Time frame: Study week 2

    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.

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

    Time frame: Study week 3

    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.

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

    Time frame: Study week 4

    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.

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

    Time frame: Study week 5

    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.

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

    Time frame: Study week 6

    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.

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

    Time frame: Study week 7

    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.

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

    Time frame: Study week 8

    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.

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

    Time frame: Study week 9

    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.

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

    Time frame: Study week 10

    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.

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

    Time frame: Study week 11

    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.

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

    Time frame: Study week 12

    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.

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

    Time frame: 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). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.

Secondary outcomes

  1. Self-reported opioid craving scores as assessed via smartphone surveys

    Time frame: Study week 1

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  2. Self-reported opioid craving scores as assessed via smartphone surveys

    Time frame: Study week 2

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  3. Self-reported opioid craving scores as assessed via smartphone surveys

    Time frame: Study week 5

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  4. Self-reported opioid craving scores as assessed via smartphone surveys

    Time frame: Study week 9

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  5. Self-reported opioid craving scores as assessed via smartphone surveys

    Time frame: 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

  6. Self-reported opioid craving scores as assessed via smartphone surveys

    Time frame: Study week 14

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  7. Self-reported opioid craving scores as assessed via smartphone surveys

    Time frame: 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

  8. Self-reported opioid craving as assessed via In-person Cravings Scales scores

    Time frame: Study week 2

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  9. Self-reported opioid craving as assessed via In-person Cravings Scales scores

    Time frame: Study week 3

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  10. Self-reported opioid craving as assessed via In-person Cravings Scales scores

    Time frame: Study week 4

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  11. Self-reported opioid craving as assessed via In-person Cravings Scales scores

    Time frame: Study week 5

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  12. Self-reported opioid craving as assessed via In-person Cravings Scales scores

    Time frame: Study week 6

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  13. Self-reported opioid craving as assessed via In-person Cravings Scales scores

    Time frame: Study week 7

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  14. Self-reported opioid craving as assessed via In-person Cravings Scales scores

    Time frame: Study week 8

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  15. Self-reported opioid craving as assessed via In-person Cravings Scales scores

    Time frame: Study week 9

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  16. Self-reported opioid craving as assessed via In-person Cravings Scales scores

    Time frame: Study week 10

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  17. Self-reported opioid craving as assessed via In-person Cravings Scales scores

    Time frame: Study week 11

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  18. Self-reported opioid craving as assessed via In-person Cravings Scales scores

    Time frame: Study week 12

    Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention

  19. Self-reported opioid craving as assessed via In-person Cravings Scales scores

    Time frame: 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

  20. Number of subjects who sustained abstinence from opioids (Binary indicator)

    Time frame: Study week 10

    Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.

  21. Number of subjects who sustained abstinence from opioids (Binary indicator)

    Time frame: Study week 11

    Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.

  22. Number of subjects who sustained abstinence from opioids (Binary indicator)

    Time frame: Study week 12

    Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.

  23. Number of subjects who sustained abstinence from opioids (Binary indicator)

    Time frame: Study week 13

    Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.

  24. Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)

    Time frame: Study week 10

    Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.

  25. Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)

    Time frame: Study week 11

    Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.

  26. Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)

    Time frame: Study week 12

    Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.

  27. Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)

    Time frame: Study week 13

    Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.

  28. Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 2

    Validated daily binary indicator for measuring use of stimulants

  29. Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 3

    Validated daily binary indicator for measuring use of stimulants

  30. Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 4

    Validated daily binary indicator for measuring use of stimulants

  31. Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 5

    Validated daily binary indicator for measuring use of stimulants

  32. Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 6

    Validated daily binary indicator for measuring use of stimulants

  33. Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 7

    Validated daily binary indicator for measuring use of stimulants

  34. Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 8

    Validated daily binary indicator for measuring use of stimulants

  35. Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 9

    Validated daily binary indicator for measuring use of stimulants

  36. Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 10

    Validated daily binary indicator for measuring use of stimulants

  37. Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 11

    Validated daily binary indicator for measuring use of stimulants

  38. Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 12

    Validated daily binary indicator for measuring use of stimulants

  39. Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 13

    Validated daily binary indicator for measuring use of stimulants

  40. Days using opioids over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 2

    Validated daily binary indicator for measuring use of opioids

  41. Days using opioids over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 3

    Validated daily binary indicator for measuring use of opioids

  42. Days using opioids over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 4

    Validated daily binary indicator for measuring use of opioids

  43. Days using opioids over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 5

    Validated daily binary indicator for measuring use of opioids

  44. Days using opioids over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 6

    Validated daily binary indicator for measuring use of opioids

  45. Days using opioids over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 7

    Validated daily binary indicator for measuring use of opioids

  46. Days using opioids over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 8

    Validated daily binary indicator for measuring use of opioids

  47. Days using opioids over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 9

    Validated daily binary indicator for measuring use of opioids

  48. Days using opioids over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 10

    Validated daily binary indicator for measuring use of opioids

  49. Days using opioids over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 11

    Validated daily binary indicator for measuring use of opioids

  50. Days using opioids over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 12

    Validated daily binary indicator for measuring use of opioids

  51. Days using opioids over the 12-week treatment period by Timeline Followback questionnaire

    Time frame: Study week 13

    Validated daily binary indicator for measuring use of opioids

Study contacts

Contact information is provided by the study sponsor or research team.

Jennifer Nyland, PhD

CONTACT

[email protected]

717-531-6172

Kirsten Shuler, MSc

CONTACT

[email protected]

717-531-4104

Sponsors and collaborators

Lead sponsor

Milton S. Hershey Medical Center

Other

Collaborators

  • National Institute on Drug Abuse (NIDA)
  • New York University
  • Stanley Street Treatment and Resources (SSTAR)
  • University of Maryland

Registry information

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Aug 12, 2024
Registry last updated
Jul 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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