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The purpose of this randomized, double-blind, placebo-controlled, multi-site clinical trial is to evaluate the safety and efficacy of tirzepatide in a sample of 100 patients diagnosed with moderate or severe CUD by DSM-5 criteria.
This is a double-blind, placebo-controlled, randomized clinical trial. 100 individuals with moderate to severe cannabis use disorder (CUD) will be randomized in a 1:1 ratio to receive either (1) weekly subcutaneous injections of tirzepatide or (2) weekly subcutaneous injections of matching placebo for 24 weeks. Tirzepatide will be initiated at 2.5 mg for 4 weeks (4 injections) and increased in 2.5 mg increments every 4 weeks as tolerated, up to a maximum dose of 15 mg.
The Primary Objective is to determine the maximum tolerated dose (MTD) of tirzepatide in individuals with CUD and to evaluate its efficacy in reducing cannabis use.
The primary Hypothesis is that tirzepatide will be well tolerated within the FDA-recommended dose range and compared with placebo, it will result in a significantly greater proportion of cannabis abstinent days as measured by the timeline follow-back (TLFB).
Secondary Objectives are to evaluate the effects of tirzepatide, relative to placebo, on (1) CUD severity based on DSM-5 criteria; (2) percentage of cannabis-negative weekly urine drug screens collected during the treatment period; (3) cannabis craving; (4) cannabis withdrawal severity; (5) retention in treatment; and (6) quality of life.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active Treatment | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tirzepatide | Drug | Participants will receive weekly injections of tirzepatide 2.5 mg for 4 weeks. The dose is expected to increase by 2.5 mg every 4 weeks, however, the decision to increase the dose will be made based on the Dose Increase Checklist and shared decision between the site study physician (MD or DO) and the participant. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) | The maximum tolerated dose defined as the median dose within the FDA-recommended range, at which dose increase is not recommended (based on standardized and health care provider assessments). | 24 weeks (Treatment Phase) |
| Days of Abstinence | Number of days per week with no cannabis use, as assessed by Timeline Follow Back (TLFB). | 24 weeks (Treatment Phase) |
| Measure | Description | Time Frame |
|---|---|---|
| Severity of Cannabis Use Disorder (CUD) | Severity of CUD as determined by DSM-5 criteria for Cannabis Use Disorder Checklist and expressed as a number of reported symptoms | 24 weeks (Treatment Phase) |
| Negative Urine Drug Screens (UDS) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jennifer Wong, PhD | Contact | 301-827-6267 | Jennifer.Wong3@nih.gov | |
| Jana Drgonova, PhD | Contact | 301-827-5933 | jana.drgonova@nih.gov |
| Name | Affiliation | Role |
|---|---|---|
| Jia Bei Wang, MD, PhD | NIDA/NIH, Division of Therapeutics and Medical Consequences (DTMC) | Principal Investigator |
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| ID | Term |
|---|---|
| D002189 | Marijuana Abuse |
| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000098860 | Tirzepatide |
| ID | Term |
|---|---|
| D000067757 | Glucagon-Like Peptide-1 Receptor |
| D000067756 | Glucagon-Like Peptide Receptors |
| D043562 | Receptors, G-Protein-Coupled |
| D011956 | Receptors, Cell Surface |
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A parallel, randomized trial with 1:1 assignment to treatment versus placebo. The starting dose of active the medication (tirzepatide) is 2.5 mg, and is expected to increase by 2.5 mg every 4 weeks based on its tolerability and participant's adherence
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|
| Placebo | Drug | Participants will receive weekly masked injections of placebo. |
|
Percentage of weekly urine drug screens testing negative for cannabis out of all scheduled weekly drug screens.
| 24 weeks (Treatment Phase) |
| Cannabis Craving | Cannabis Craving as assessed by the short form of the Marijuana Craving Questionnaire (MCQ) and expressed as a score. The score range is 12-84, and the higher score indicates a higher or more frequent level of craving. | 24 weeks (Treatment Phase) |
| 1. Cannabis Withdrawal | Cannabis withdrawal as assessed by the DSM 5 Cannabis Withdrawal Checklist and expressed as a number of symptoms present (up to 7) | 24 weeks (Treatment Phase) |
| Retention in Treatment | Percentage of randomized participants who receive study medication during the treatment phase. | Week 24 (End of Treatment Phase) |
| Quality of Life | Quality of life (physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, and pain intensity) as determined by PROMIS-29 questionnaire and expressed as a score. The domain scores (T-scores) range is 20-80 with higher scores representing better outcomes. | 24 weeks (Treatment Phase) |
| D008565 | Membrane Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011964 | Receptors, Gastrointestinal Hormone |
| D018000 | Receptors, Peptide |