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| ID | Type | Description | Link |
|---|---|---|---|
| UH3DA050325 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| New York University | OTHER |
| University of Maryland | OTHER |
| National Institute on Drug Abuse (NIDA) | NIH |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Control group | Placebo Comparator | Participants in the control group will have placebo administered once per week. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Semaglutide Pen Injector | Drug | Semaglutide will be provided using an injection pen |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of participants being abstinent from illicit and nonprescribed opioids. | Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage. | Study week 2 |
| Number of participants being abstinent from illicit and nonprescribed opioids. | Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage. | Study week 3 |
| Number of participants being abstinent from illicit and nonprescribed opioids. | Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage. | Study week 4 |
| Number of participants being abstinent from illicit and nonprescribed opioids. | Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Study week 1 |
| Self-reported opioid craving scores as assessed via smartphone surveys |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jennifer Nyland, PhD | Contact | 717-531-6172 | jnyland@pennstatehealth.psu.edu | |
| Kirsten Shuler, MSc | Contact | 717-531-4104 | kshuler@pennstatehealth.psu.edu |
| Name | Affiliation | Role |
|---|---|---|
| Jennifer Nyland, PhD | Milton S. Hershey Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Maryland Baltimore | Recruiting | Baltimore | Maryland | 21223 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41168808 | Derived | Freet CS, Shuler K, Kawasaki S, Weintraub E, Greenblatt A, Kladney M, Nunes E, Foster KL, Kong L, Raja-Khan N, Cleveland HH, Grigson PS, Bunce SC, Brick TR, Nyland JE. Efficacy of the GLP-1 receptor agonist, semaglutide, in abstinence from illicit and nonprescribed opioids in an outpatient population with 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. | |
| 40502777 |
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Only summary data will be made available. No individual participant data (IPD) will be shared with other researchers.
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| Placebo | Drug | Placebo will be a dry needle stick; no substances will be injected |
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| Study week 5 |
| Number of participants being abstinent from illicit and nonprescribed opioids. | Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage. | Study week 6 |
| Number of participants being abstinent from illicit and nonprescribed opioids. | Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage. | Study week 7 |
| Number of participants being abstinent from illicit and nonprescribed opioids. | Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage. | Study week 8 |
| Number of participants being abstinent from illicit and nonprescribed opioids. | Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage. | Study week 9 |
| Number of participants being abstinent from illicit and nonprescribed opioids. | Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage. | Study week 10 |
| Number of participants being abstinent from illicit and nonprescribed opioids. | Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage. | Study week 11 |
| Number of participants being abstinent from illicit and nonprescribed opioids. | Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage. | Study week 12 |
| Number of participants being abstinent from illicit and nonprescribed opioids. | Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage. | Study week 13 |
Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention |
| 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | Study week 13 |
| NYU Langone Health | Recruiting | New York | New York | 10016 | United States |
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| Pennsylvania Psychiatric Institute | Recruiting | Harrisburg | Pennsylvania | 17110 | United States |
|
| Freet CS, Shuler K, Kawasaki S, Weintraub E, Greenblatt A, Kladney M, Nunes E, Foster KL, Kong L, Raja-Khan N, Cleveland HH, Grigson PS, Bunce SC, Brick TR, Nyland JE. Efficacy of the GLP-1 receptor agonist, semaglutide, in abstinence from illicit and nonprescribed opioids in an outpatient population with treatment-refractory OUD: A randomized, double-blind, placebo-controlled clinical trial protocol. Res Sq [Preprint]. 2025 May 26:rs.3.rs-6666196. doi: 10.21203/rs.3.rs-6666196/v1. |
| ID | Term |
|---|---|
| D009293 | Opioid-Related Disorders |
| D016739 | Behavior, Addictive |
| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
| ID | Term |
|---|---|
| D003192 | Compulsive Behavior |
| D007175 | Impulsive Behavior |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| C000591245 | semaglutide |
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