Evaluation of Tirzepatide as an Adjunct to Buprenorphine for the Treatment of Opioid Use Disorder

NCT ID: NCT06651177

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

310 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-12

Study Completion Date

2027-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Opioid Use Disorder Opioid Use Disorder, Moderate Opioid Use Disorder, Severe

Keywords

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tirzepatide opioid opioid use disorder buprenorphine GLP-1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Tirzepatide

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.

Group Type EXPERIMENTAL

Tirzepatide

Intervention Type DRUG

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

Placebo

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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.

Interventions

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Tirzepatide

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

Intervention Type DRUG

Placebo

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.

Intervention Type OTHER

Other Intervention Names

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Mounjaro Zepbound

Eligibility Criteria

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Inclusion Criteria

1. Must be ≥18 years of age;
2. Must have moderate to severe OUD;
3. Must, at the time of randomization, be newly initiated on BUP (i.e., within 7 to 28 days) during the current treatment episode, be taking ≥ the recommended target dose for transmucosal BUP (or equivalent for extended-release), and have documentation of receiving BUP, including dose and the start date of the current treatment episode, from their BUP provider;
4. Must be willing to be randomized to tirzepatide or placebo and to comply with study procedures, including weekly visits for 6 months;
5. Must be able to understand the study, and having understood, provide written informed consent in English;
6. 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:

1. infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, tubal implants, or tubal ligation), congenital anomaly such as Mullerian agenesis; are
2. post-menopausal defined as ≥ 55 years old not on hormone therapy, who has had at least 12 months of spontaneous amenorrhea;
3. ≥ 55 years old with a diagnosis of menopause prior to starting hormone replacement therapy; or
4. ≥ 40 years old with an intact uterus, not on hormone therapy, who has cessation of menses for at least 1 year without an alternative medical cause, AND a follicle-stimulating hormone ≥ 40 mIU/mL; participants in this category must test negative on the study-administered pregnancy test(s).

Exclusion Criteria

1. have a history of type 1 or type 2 diabetes mellitus (other than pregnancy-related diabetes);
2. have a BMI \<25.0;
3. have any of the following cardiovascular conditions within 90 days prior to signing consent: acute myocardial infarction, cerebrovascular accident (stroke), unstable angina, or hospitalization due to congestive heart failure (CHF);
4. have a known history of chronic or acute pancreatitis, gallbladder disease, gastroparesis, gastric emptying abnormality, gastroesophageal reflux disease, or other severe gastrointestinal disease;
5. have a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2);
6. have previously taken tirzepatide, have taken any GLP-1 analogue within the 6 months before consent, or have a known history of prior hypersensitivity reaction to any GLP-1 analogue;
7. have renal impairment defined as an estimated glomerular filtration rate (eGFR) value of \< 15 mL/min/1.73 m2 or requiring dialysis;
8. have a current, or within the 30 days prior to signing consent, use of, or plan to start during the course of the trial:

1. medications with glucose lowering properties: GLP-1 analogs, sulfonylurea, insulin, metformin, thiazolidinediones, dipeptidyl peptidase-4 (DPP-IV) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors;
2. systemic steroids including prednisone, hydrocortisone, dexamethasone;
9. have a history of suicide attempts or significant active suicidal ideation as assessed by a qualified study clinician;
10. have a psychiatric or medical condition that, in the judgment of the site medical clinician (BMC or UMC), would make study participation unsafe or which would make treatment compliance difficult;
11. have current status as a prisoner OR be currently in jail, prison, or any inpatient overnight facility as required by court of law or have pending legal action or other situation (e.g., unstable living arrangements) that, in the judgement of the site investigator, could prevent participation in the study or in any study activities.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

T. John Winhusen, PhD

OTHER

Sponsor Role lead

Responsible Party

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T. John Winhusen, PhD

Professor; Vice Chair and Division Director of Addiction Sciences

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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T. John Winhusen, PhD.

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Locations

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Tarzana Treatment Centers

Tarzana, California, United States

Site Status NOT_YET_RECRUITING

Gateway Community Services

Jacksonville, Florida, United States

Site Status NOT_YET_RECRUITING

IBIS Behavioral Health

Tampa, Florida, United States

Site Status NOT_YET_RECRUITING

Ruth M. Rothstein CORE Center

Chicago, Illinois, United States

Site Status NOT_YET_RECRUITING

The Gibson Center for Behavioral Change

Cape Girardeau, Missouri, United States

Site Status NOT_YET_RECRUITING

Prisma Health

Greenville, South Carolina, United States

Site Status NOT_YET_RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

University of Utah

Salt Lake City, Utah, United States

Site Status NOT_YET_RECRUITING

Marshall Health

Huntington, West Virginia, United States

Site Status NOT_YET_RECRUITING

Healthy Minds/Chestnut Ridge

Morgantown, West Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Frankie B Kropp, MS, LICDC

Role: CONTACT

Phone: 513-585-8290

Email: [email protected]

Benjamin T Kropp, MSLS

Role: CONTACT

Phone: 513-585-8287

Email: [email protected]

Facility Contacts

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Clarita Lantican, PhD.

Role: primary

Tolib Rakhmanov

Role: backup

Candace Hodgkins, PhD.

Role: primary

Joseph Seim

Role: backup

Frank Melo, MD

Role: primary

Pamela Vergara-Rodriguez, MD

Role: primary

Mireya Gonzalez

Role: backup

Ashley Naeger

Role: primary

Alain Litwin, MD

Role: primary

Anthony Faso

Role: backup

Jessica L Young, MD

Role: primary

Stephanie Hartwig

Role: backup

Marcela Smid, MD, MS, MA

Role: primary

Grace Humiston

Role: backup

Zachary Hansen, MD

Role: primary

Lacey Andrews

Role: backup

Laura Lander, MSW, LICSW

Role: primary

Michelle Chisester

Role: backup

Other Identifiers

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UG1DA013732

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2024-1003

Identifier Type: -

Identifier Source: org_study_id