Opioid Use DisorderPhase 2NCT06548490
GLP-1R Agonist Treatment for Opioid Use Disorder
A Phase 2 study testing Semaglutide Pen Injector in people with Opioid Use Disorder and Opioid Abuse and Addiction, run by Milton S. Hershey Medical Center at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Opioid Use Disorder, Opioid Abuse and Addiction, Narcotic-Related Disorders
- What is being tested?
- Semaglutide Pen Injector
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 4 sitesUnited States
- Study dates
- 27 Jan 2025to 30 Apr 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Show all 24Show fewer
- 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.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 3 recruiting
- Completed
University of Maryland Baltimore
Baltimore, Maryland, 21223
- Recruiting
Stanley Street Treatment and Resources
Fall River, Massachusetts, 02720
Research Hotline, 508-324-3522, Research@sstar.org
Genie Bailey
- Recruiting
Pennsylvania Psychiatric Institute
Harrisburg, Pennsylvania, 17110
Subi Upadhyay, supadhyay1@pennstatehealth.psu.edu
Angela Spangler, (717) 683-7838, aspangler@pennstatehealth.psu.edu
- Recruiting
NYU Langone Health
New York, New York, 10016
Mat Kladney, 929 573 0673, mathew.kladney@nyulangone.org
Mathew Kladney, MD
About this study
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?
Read more
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
Read the 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 (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.
- Conditions
- Opioid Use Disorder, Opioid Abuse and Addiction, Narcotic-Related Disorders, Substance-Related Disorders, Chemically-Induced Disorders, Mental Disorder
- Being tested
- Semaglutide Pen Injector, Placebo
- Keywords
- Opiate treatment, Opioid treatment, Glucagon-Like Peptide-1 Agonist, Opioid use disorder, Semaglutide
- Medical subject headings
- Opioid-Related Disorders, Behavior, Addictive, Narcotic-Related Disorders, Substance-Related Disorders, Chemically-Induced Disorders, Mental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semaglutide Pen InjectorDrug
Also called Ozempic
Semaglutide will be provided using an injection pen
PlaceboDrug
Also called Dry needle stick
Placebo will be a dry needle stick; no substances will be injected
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Semaglutide Pen Injector |
| Control group | Placebo comparator | Participants in the control group will have placebo administered once per week. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Study week 13
Secondary outcomes (51)
Self-reported opioid craving scores as assessed via smartphone surveys
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 1
Self-reported opioid craving scores as assessed via smartphone surveys
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 2
Self-reported opioid craving scores as assessed via smartphone surveys
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 5
Self-reported opioid craving scores as assessed via smartphone surveys
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 9
Self-reported opioid craving scores as assessed via smartphone surveys
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 13
Self-reported opioid craving scores as assessed via smartphone surveys
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 14
Self-reported opioid craving scores as assessed via smartphone surveys
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 18
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 2
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 3
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 4
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 5
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 6
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 7
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 8
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 9
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 10
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 11
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 12
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention
Measured: Study week 13
Number of subjects who sustained abstinence from opioids (Binary indicator)
Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.
Measured: Study week 10
Number of subjects who sustained abstinence from opioids (Binary indicator)
Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.
Measured: Study week 11
Number of subjects who sustained abstinence from opioids (Binary indicator)
Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.
Measured: Study week 12
Number of subjects who sustained abstinence from opioids (Binary indicator)
Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.
Measured: Study week 13
Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)
Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.
Measured: Study week 10
Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)
Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.
Measured: Study week 11
Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)
Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.
Measured: Study week 12
Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)
Weekly abstinence rating (see primary outcome above) is rated as abstinent over the last 4 weeks for the treatment period.
Measured: Study week 13
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of stimulants
Measured: Study week 2
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of stimulants
Measured: Study week 3
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of stimulants
Measured: Study week 4
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of stimulants
Measured: Study week 5
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of stimulants
Measured: Study week 6
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of stimulants
Measured: Study week 7
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of stimulants
Measured: Study week 8
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of stimulants
Measured: Study week 9
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of stimulants
Measured: Study week 10
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of stimulants
Measured: Study week 11
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of stimulants
Measured: Study week 12
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of stimulants
Measured: Study week 13
Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of opioids
Measured: Study week 2
Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of opioids
Measured: Study week 3
Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of opioids
Measured: Study week 4
Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of opioids
Measured: Study week 5
Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of opioids
Measured: Study week 6
Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of opioids
Measured: Study week 7
Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of opioids
Measured: Study week 8
Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of opioids
Measured: Study week 9
Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of opioids
Measured: Study week 10
Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of opioids
Measured: Study week 11
Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of opioids
Measured: Study week 12
Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
Validated daily binary indicator for measuring use of opioids
Measured: Study week 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2024
- Study start27 Jan 2025
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- New York University, University of Maryland, National Institute on Drug Abuse (NIDA), Stanley Street Treatment and Resources (SSTAR)
- Responsible party
- Principal investigator, Patricia Sue Grigson, Milton S. Hershey Medical Center
- Investigators
- Jennifer Nyland, PhD, Principal investigator, Milton S. Hershey Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06548490
- Sponsor's protocol ID
- STUDY00024676
- Other IDs
- UH3DA050325
- Status last verified
- Aug 2026
- First submitted
- 7 Aug 2024
- Last updated
- 28 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Only summary data will be made available. No individual participant data (IPD) will be shared with other researchers.
Publications
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.
PubMed 41168808Freet 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.
PubMed 40502777
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GLP-1R Agonist Treatment for Opioid Use Disorder
- ClinicalTrials.gov ID
- NCT06548490
- Acronym / sponsor ID
- STUDY00024676
- Conditions
- Opioid Use Disorder, Opioid Abuse and Addiction, Narcotic-Related Disorders, Substance-Related Disorders, Chemically-Induced Disorders, Mental Disorder
- Keywords
- Opiate treatment, Opioid treatment, Glucagon-Like Peptide-1 Agonist, Opioid use disorder, Semaglutide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Collaborators
- New York University, University of Maryland, National Institute on Drug Abuse (NIDA), Stanley Street Treatment and Resources (SSTAR)
- Study start
- 27 Jan 2025 (actual)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 12 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 (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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Investigational group | Experimental | Drug: Semaglutide Pen InjectorParticipants 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 comparator | Drug: PlaceboParticipants in the control group will have placebo administered once per week. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Semaglutide Pen InjectorAlso: OzempicSemaglutide will be provided using an injection pen | Drug | Investigational group |
| PlaceboAlso: Dry needle stickPlacebo will be a dry needle stick; no substances will be injected | Drug | Control group |
Primary outcome
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
51 secondary outcomes
Self-reported opioid craving scores as assessed via smartphone surveys
Time frame: Study week 1
Self-reported opioid craving scores as assessed via smartphone surveys
Time frame: Study week 2
Self-reported opioid craving scores as assessed via smartphone surveys
Time frame: Study week 5
Self-reported opioid craving scores as assessed via smartphone surveys
Time frame: Study week 9
Self-reported opioid craving scores as assessed via smartphone surveys
Time frame: Study week 13
Self-reported opioid craving scores as assessed via smartphone surveys
Time frame: Study week 14
Self-reported opioid craving scores as assessed via smartphone surveys
Time frame: Study week 18
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Time frame: Study week 2
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Time frame: Study week 3
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Time frame: Study week 4
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Time frame: Study week 5
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Time frame: Study week 6
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Time frame: Study week 7
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Time frame: Study week 8
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Time frame: Study week 9
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Time frame: Study week 10
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Time frame: Study week 11
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Time frame: Study week 12
Self-reported opioid craving as assessed via In-person Cravings Scales scores
Time frame: Study week 13
Number of subjects who sustained abstinence from opioids (Binary indicator)
Time frame: Study week 10
Number of subjects who sustained abstinence from opioids (Binary indicator)
Time frame: Study week 11
Number of subjects who sustained abstinence from opioids (Binary indicator)
Time frame: Study week 12
Number of subjects who sustained abstinence from opioids (Binary indicator)
Time frame: Study week 13
Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)
Time frame: Study week 10
Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)
Time frame: Study week 11
Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)
Time frame: Study week 12
Number of subjects abstinent from stimulants (i.e. cocaine or non-prescribed amphetamines) (Binary indicator)
Time frame: Study week 13
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Time frame: Study week 2
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Time frame: Study week 3
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Time frame: Study week 4
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Time frame: Study week 5
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Time frame: Study week 6
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Time frame: Study week 7
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Time frame: Study week 8
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Time frame: Study week 9
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Time frame: Study week 10
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Time frame: Study week 11
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Time frame: Study week 12
Days using stimulants over the 12-week treatment period by Timeline Followback questionnaire
Time frame: Study week 13
Days using opioids over the 12-week treatment period by Timeline Followback questionnaire
Time frame: Study week 2
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2026.
- Derived from this study: PubMed 41168808Freet 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.
- Derived from this study: PubMed 40502777Freet 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.
- Individual participant dataSharing planned: No. Only summary data will be made available. No individual participant data (IPD) will be shared with other researchers.
Related trials for Opioid Use Disorder
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Enrolling by invitationObservational study
Development of an Interview-Informed Timeline Follow-Back (TLFB) for Opioid Use in the Era of Fentanyl
Substance Use Disorders (SUDs)
Not yet recruiting
Comprehensive Opioid Management and Breathing During Sleep
Sleep-Disordered Breathing, Chronic Opioid Use
Active, not recruitingPhase 2
Wellcome Leap Psilocybin for OUD
Opioid Use Disorder
Recruiting
Opioid and Pain Treatment in Indigenous Communities (OPTIC) Trial
Opioid Use Disorder, Opioid Misuse
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jennifer Nyland, PhD principal investigator
Milton S. Hershey Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Semaglutide Pen Injector in people with Opioid Use Disorder and Opioid Abuse and Addiction, run by Milton S. Hershey Medical Center at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jennifer Nyland, PhD (717-531-6172, jnyland@pennstatehealth.psu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants being abstinent from illicit and nonprescribed opioids. (time frame: Study week 2). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06548490, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2026.