A Phase 2 interventional study of Tirzepatide and Placebo in Opioid Use Disorder, Opioid Use Disorder, Moderate and Opioid Use Disorder, Severe, sponsored by T. John Winhusen, PhD. Recruiting at 9 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-11.
Sponsored by T. John Winhusen, PhD · Phase 2, Interventional, and Treatment
The primary objective of this research study is to evaluate the effect of tirzepatide, relative to placebo, as an adjunct to BUP on retention, substance use, and sleep outcomes in individuals with OUD.
This is a Phase 2, pragmatic, multi-site, double-blind, randomized, placebo-controlled, intent-to-treat trial. The selection of placebo as the comparator is considered the gold standard for medication trials. Eligible participants will be randomized in a 1:1 ratio to tirzepatide or placebo, balancing on site and buprenorphine (BUP) formulation (transmucosal vs extended-release).
Participants will receive tirzepatide or placebo based on randomized assignment, with "dose escalation" of placebo following the schedule for tirzepatide and tirzepatide dosing being consistent with prescribing guidelines. Participants will be administered a subcutaneous (SQ) study medication injection weekly and attend weekly research visits through 26 weeks post-randomization with longer research visits at 1, 3, and 6 months post-randomization. A follow-up visit for final safety measures will be completed at week 30, which takes into account tirzepatide's long half-life.
Duration of participation will be approximately 31 weeks for study participants. Participants will be administered study medication and attend weekly research visits through 6 months post-randomization with longer research visits at 1-, 3-, and 6-months post-randomization. Participants will be provided with a Fitbit to measure sleep. BUP is not a study medication; participants will receive BUP through their clinical provider. A follow-up visit for final safety measures will be completed at week 30.
Must not be breastfeeding; if of child bearing potential, must test negative on the study-administered pregnancy test(s), and if of childbearing potential and engaging /planning to engage in sexual intercourse must agree to effective contraception for the duration of the trial through 30 days after the trial; effective contraception is defined as using: a) birth control injection, an intrauterine device, or implant; or b) two birth control methods - for example birth control pills with a barrier method (e.g., condoms, etc.).
If ever of childbearing potential, a participant is considered to not be of childbearing potential for the study if they are:
Exclusion Criteria:
have a current, or within the 30 days prior to signing consent, use of, or plan to start during the course of the trial:
The tirzepatide pen is a pre-filled, disposable, injection device designed for subcutaneous administration. Each pen is pre-filled with a single dose of tirzepatide and is available in six doses: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg/0.5 mL. An unblinded study MC (UMC) will administer the once-weekly SQ dose of tirzepatide. Consistent with tirzepatide's prescribing guidelines, participants will be initiated at a once-weekly SQ dose of 2.5 mg/week with a dose increase to 5mg/week at week 5. Consistent with tirzepatide's prescribing information, once the participant has received 5 mg/week for 4 weeks they are eligible for a dose increase if needed.
Drug: Tirzepatide
Saline administered subcutaneously with a syringe will be used as the placebo for the trial. The placebo which will be administered by a study UMC. The process for deciding on "dose increases" will be the same for placebo and tirzepatide.
Other: Placebo
The tirzepatide pen is a pre-filled, disposable, injection device designed for subcutaneous administration. Each pen is pre-filled with a single dose of tirzepatide and is available in six doses: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg/0.5 mL. A UMC will administer the once-weekly SQ dose of tirzepatide. Consistent with tirzepatide's prescribing guidelines, participants will be initiated at a once-weekly SQ dose of 2.5 mg/week with a dose increase to 5mg/week at week 5. Consistent with tirzepatide's prescribing information, once the participant has received 5 mg/week for 4 weeks they are eligible for a dose increase if needed
Also known as: Mounjaro, Zepbound
Saline administered subcutaneously with a syringe will be used as the placebo for the trial. The placebo which will be administered by a study UMC. The process for deciding on "dose increases" will be the same for placebo and tirzepatide.
6-month retention in BUP treatment
MOUD is defined as buprenorphine (BUP). The receipt of BUP will be assessed thorough self-report collected through a Timeline Follow-Back (TLFB) procedure and will be partially verified through urine drug screens.
Time frame: 6 months
Proportion of illicit opioid-negative urine samples during the 6-month active treatment phase
A rapid Urine Drug Screen (UDS)UDS system will be used to analyze the urine samples. Illicit opioid-negative UDSs are defined as being negative for fentanyl, opiates, oxycodone, and methadone (unless the participant starts methadone treatment).
Time frame: 6 Months
Proportion of UDS negative for non-opioid (and cotinine) drugs and alcohol
A rapid Urine Drug Screen (UDS)UDS system will be used to analyze the urine samples. Negative urine samples are defined as being negative for: cocaine, methamphetamine, amphetamine, marijuana, benzodiazepines, methylenedioxymethamphetamine, barbiturates, phencyclidine, and ethyl glucuronide.
Time frame: 6 months
Treatment Effectiveness
Treatment Effectiveness will be measured by the Treatment Effectiveness Assessment (TEA). The TEA is a patient-oriented instrument that assesses the participant's perceived improvements in substance use, health, ability to fulfill adult obligations, and to be a good community member. The TEA includes four items, each rated on a 1-10-point scale (from none to much better) yielding a total score of 4-40.
Time frame: 6 months
Sleep Quality - Fitbit Charge 6™ (FBC-6)
An objective measure of the impact of tirzepatide, relative to placebo, on sleep will be obtained using the Fitbit Charge 6™ (FBC-6). A comparison of an earlier version of the device (Fitbit Charge 4™) to polysomnography found no significant differences in the measures of total sleep time and waking after sleep onset. Each participant will be provided with a Fitbit Charge 6™ when they are deemed eligible for randomization and asked to wear it every night (or whenever they have their longer period of intended sleep) through the final study visit. Data from the Fitbit Charge 6™ will be downloaded at the weekly research visits. Total sleep time is the main outcome of interest.
Time frame: 6 months
Sleep Quality - The Pittsburgh Sleep Quality Index (PSQI)
Participant perceived sleep quality will be assessed using the PSQI, which is a relatively brief, validated instrument that measures sleep quality.
Time frame: 6 months
Plan to share: Yes — De-identified participant-level data gathered from case report forms.
Supporting information: Study protocol, Sap, Icf, Csr, Analytic code
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T. John Winhusen, PhD