Tirzepatide with buprenorphine for opioid use disorder

NIDA CTN-0152: Evaluation of Tirzepatide as an Adjunct to Buprenorphine for the Treatment of Opioid Use Disorder: A Pragmatic, Multi-site, Double-blind, Randomized, Placebo-controlled Trial (TAB)

This trial will test whether adding weekly tirzepatide injections to buprenorphine helps adults with moderate to severe opioid use disorder stay in treatment, reduce opioid use, and improve sleep.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 310 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Cincinnati (other)
• Drugs / interventions: prednisone
• Locations: 10 sites (Tarzana, California and 9 other locations)
• Trial ID: NCT06651177 on ClinicalTrials.gov

What this trial studies

This is a Phase 2, multi-site, double-blind, randomized, placebo-controlled trial testing tirzepatide as an adjunct to buprenorphine in adults with moderate-to-severe opioid use disorder. Eligible participants who recently started buprenorphine (7–35 days) are randomized 1:1 to weekly subcutaneous tirzepatide or matching placebo with dose escalation following the drug schedule. Participants attend weekly research visits through 26 weeks with longer assessments at 1, 3, and 6 months and a final safety follow-up at week 30, and wear a Fitbit to capture sleep outcomes. The trial uses intent-to-treat analysis and balances randomization by site and buprenorphine formulation (transmucosal vs extended-release).

Who should consider this trial

Good fit: Adults (≥18) with moderate-to-severe opioid use disorder who started buprenorphine 7–35 days ago, are on the recommended buprenorphine dose, and can commit to weekly visits and injections are ideal candidates.

Not a fit: People not on buprenorphine, those who started buprenorphine outside the 7–35 day window, pregnant or breastfeeding individuals, or those unable to attend weekly in-person visits are unlikely to benefit from participating.

Why it matters

Potential benefit: If successful, adding tirzepatide could improve retention in buprenorphine treatment, reduce opioid use, and improve sleep for people with opioid use disorder.

How similar studies have performed: GLP-1–based drugs have shown promising signals in preclinical and early human studies for reducing substance use, but using tirzepatide specifically as an adjunct for OUD is largely novel and untested in large clinical trials.

Eligibility criteria

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 35 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, and, for participants prescribed transmucosal BUP, have at least one UDS positive for buprenorphine/norbuprenorphine;
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 in the prior year 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.

Where this trial is running

Tarzana, California and 9 other locations

• Tarzana Treatment Centers — Tarzana, California, United States (NOT_YET_RECRUITING)
• Gateway Community Services — Jacksonville, Florida, United States (RECRUITING)
• IBIS Behavioral Health — Tampa, Florida, United States (NOT_YET_RECRUITING)
• Ruth M. Rothstein CORE Center — Chicago, Illinois, United States (RECRUITING)
• The Gibson Center for Behavioral Change — Cape Girardeau, Missouri, United States (RECRUITING)
• Prisma Health — Greenville, South Carolina, United States (RECRUITING)
• Vanderbilt University Medical Center — Nashville, Tennessee, United States (RECRUITING)
• University of Utah — Salt Lake City, Utah, United States (RECRUITING)
• Marshall Health — Huntington, West Virginia, United States (RECRUITING)
• Healthy Minds/Chestnut Ridge — Morgantown, West Virginia, United States (RECRUITING)

Study contacts

• Principal investigator: T. John Winhusen, PhD. — University of Cincinnati
• Study coordinator: Frankie B Kropp, MS, LICDC

Conditions: Opioid Use Disorder, Opioid Use Disorder, Moderate, Opioid Use Disorder, Severe, tirzepatide, opioid, opioid use disorder, buprenorphine, GLP-1