Methamphetamine Use Disorder
Conditions
Keywords
methamphetamine, MUD, methamphetamine use disorder, tirzepatide, substance use, GLP-1
Brief summary
This is a phase 2, randomized, double-blind, placebo-controlled, parallel-group trial evaluating the tolerability, safety, and preliminary efficacy of tirzepatide for the treatment of individuals with moderate or severe MtUD. The central hypothesis of the proposed research is that tirzepatide is a safe and potentially efficacious treatment of MtUD. Participants will undergo study procedures over 32 weeks, including: 1. completing self-assessments 2. undergo brief physical and review of medical and psychiatric history 3. provide urine and blood samples 4. medical management sessions 5. weekly subcutaneous study medication injections
Detailed description
Methamphetamine use disorder (MtUD) affects over 1.5 million U.S. adults annually and has no FDA-approved treatments. Preclinical studies and observational data suggest that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may reduce stimulant use. Tirzepatide, a dual GLP-1/glucose-dependent insulinotropic peptide (GIP) receptor agonist approved for type 2 diabetes and weight management, has not been evaluated for MtUD in an adequately-powered randomized controlled trial. This Phase 2 double-blind, randomized controlled trial will enroll 228 adults with moderate or severe MtUD to receive weekly subcutaneous tirzepatide (2.5 mg/week titrated to 15 mg/week or maximally tolerated dose) or placebo for 26 weeks, followed by 6 weeks of follow-up. Safety will be monitored throughout. The study aims are to: (1) assess tolerability (treatment discontinuation) and safety (serious adverse events) of tirzepatide; and (2) evaluate preliminary efficacy, including reduction in methamphetamine use (Timeline Follow-back), treatment response (≥6 of 8 UDS negative in weeks 23-26), and early remission (no longer meeting DSM-5 criteria at week 26). Secondary/exploratory aims include assessing reductions in methamphetamine craving and cravings for other substances.
Interventions
DRUGTirzepatide
Eligible participants who are randomized to treatment group will receive once-weekly subcutaneous injections of tirzepatide for a 26-week period. Tirzepatide will start at 2.5 mg/week with planned dose increases every four weeks in 2.5 mg/week increments up to a maximum of 15 mg/week (or the maximally tolerated dose).
DRUGPlacebo (saline)
Eligible participants who are randomized to placebo group will receive once-weekly subcutaneous injections of saline for a 26-week period.
Sponsors
University of Texas Southwestern Medical Center
National Institute on Drug Abuse (NIDA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, Double-Blind, Placebo-Controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* be aged 18 to 65 years; * have moderate or severe methamphetamine use disorder; * have active pattern of methamphetamine use; * be interested in reducing or stopping methamphetamine use; * be able and willing to provide informed consent, comply with all study procedures, and adhere to weekly study medication injections; * be overweight or obese (body mass index ≥25 kg/m²); and * (only for biological females) agree to use acceptable contraception and undergo urine pregnancy testing unless unable to become pregnant
Exclusion criteria
* report using any glucagon like peptide 1 receptor agonists (GLP-1RA, including tirzepatide), sulfonylureas, or insulin in the past 90 days; * have a current eating disorder or severe alcohol or substance use disorder; * have personal or family history of medullary thyroid carcinoma, history of multiple endocrine neoplasia type 2, or hypersensitivity, angioedema, or anaphylaxis to GLP-1RAs or tirzepatide; * have Stage 3 or higher chronic kidney disease, inadequately controlled diabetes, history of diabetic retinopathy, any unstable or serious medical or psychiatric condition, or any other reason or clinical condition that may either interfere with study participation or make the study participation unsafe (per investigator judgement); * are currently pregnant, breastfeeding, or planning pregnancy; * have received an investigational drug within 30 days of informed consent; * require psychiatric hospitalization; * have recent suicidal or current homicidal ideation; * are incarcerated or in court-mandated residential placement; * have unsafe use of alcohol, benzodiazepines, sedative/hypnotics, or other substances; or * have use of concurrent medications that may pose safety risks or interfere with study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment response | 26 weeks | Proportion of participants who attain treatment response (≥6 of 8 urine drug screens (UDS) negative for methamphetamine in Weeks 23 to 26). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability - stopping of treatment | 26 weeks | Proportion of participants discontinuing or stopping treatment before Week 26 visit. |
| Current craving for methamphetamine | 27 weeks | Severity score (range: 0-70) on stimulant craving questionnaire, higher score reflects more severe craving. |
| Early remission | 27 weeks | Proportion of participants no longer meeting DSM-5 criteria for at least 3 months (criterion for craving permitted) at the Week 27 visit. |
| Safety - occurrence of serious adverse event | 26 weeks | Proportion of participants with the occurrence of serious adverse event any time on or after Week 1 visit that is deemed to be related to study drug. |
| Reduction in self-reported use of methamphetamine | 26 weeks | From first day of Week 1 to last day of Week 26, participant's use of methamphetamine will be recorded as a binary variable (yes/no), and compared across the two treatment arms. |
| Worst past-week craving for methamphetamine | 27 weeks | Visual analog scale (VAS) for drug craving for methamphetamine, rated on 0-100, higher score indicates more severe craving |
Countries
United States
Contacts
CONTACTElizabeth Dedrick, BS
CONTACTShavonna Williams
PRINCIPAL_INVESTIGATORManish Jha, MBBS
University of Texas Southwestern Medical Center
Outcome results
None listed