Clinical trial NCT06727331: Study of Tirzepatide for Recovery and Alcohol Use Management
Official title: Tirzepatide for the Treatment of Alcohol Use Disorder: A Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Alcohol Use Disorder (AUD)
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2024-12-10
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a pilot, 4-week, double-blind, placebo-controlled, randomized trial of individuals with alcohol use disorder (AUD) to receive weekly injections of either tirzepatide (n=10) or matching placebo (n=10). The primary aim is to determine the effects of tirzepatide on cue-reactivity among individuals with AUD. The secondary aim is to assess the safety and preliminary efficacy of tirzepatide for AUD.

Detailed description: Participants include N=20 men and women with DSM5 diagnosis of AUD. Potential participants will be screened and enrolled only if they meet full inclusion criteria. After screening and baseline procedures (Visits 1 and 2) are complete, participants will be randomized to receive either tirzepatide or placebo. Following randomization, participants will be scheduled for five study visits (Visits 3-7). Each visit will last approximately 1 hour, except for study visits 2 and 7 which will take no more than 3 hours in order to conduct additional neurocognitive testing, including cue-induced cravings and decision-making tests. At visits 2-7, participants will complete vital signs, weight, urine toxicology testing, a blood draw for glucose, and questionnaires probing secondary outcomes (i.e. anxiety and depression, suicidality, substance use, opioid withdrawal symptoms, cravings, etc). At study visits 3-6, the weekly dose of tirzepatide or placebo will be administered, and assessment of adverse events will also be completed. Both participants and study staff (including raters) will be blinded to active drug vs. placebo. At visit 2, subjects' expectations about their potential treatment will be queried. The final visit, visit 7, also called the follow-up visit, will also assess subjects' guess as to which treatment they received. The medication will be purchased from the manufacturer and stored by IDS. The IDS will extract the tirzepatide and draw the dose into syringes, which will match visually with the placebo doses.

Eligibility criteria: Inclusion Criteria:

* English speaking adults aged 18 and above
* Admitted to the inpatient withdrawal management at Brigham and Women's Faulkner Hospital (BWF) Addiction Recovery Program (ARP) for the treatment of alcohol withdrawal.
* Diagnosed with current DSM-5 alcohol use disorder
* Willing and able to physically travel to BWH CCI outpatient facilities for study visits after discharge from the BWF ARP.

Exclusion Criteria:

* DSM-5 diagnosis of any current substance use disorder excluding alcohol, cannabis or tobacco
* CIWA score at screening ≥ 8.
* Psychotic disorder, active suicidality or homicidality or any psychiatric condition that impair ability to provide informed consent
* Any lifetime diagnosis of eating disorders including anorexia, bulimia, binge eating, or avoidant/restrictive food intake disorder
* BMI\<25mg/kg2
* Current or lifetime diagnosis of Type 1 or Type 2 diabetes
* Current (or within 30 days of enrollment) use of any medications for AUD (naltrexone, acamprosate, disulfiram, gabapentin, etc.), any anti-obesity medications, or medications with glucose lowering properties (including GLP-1 analogues, sulfonylurea, insulin, metformin, thiazolidinediones, dipeptidyl peptidase-4 (DPP-IV) inhibitors, or sodium-glucose cotransporter-2 (SGLT-2) inhibitors)
* Use of any GLP-1 agonist medications in the prior 3 months
* Anticipating receipt of any other GLP-1 agonist medications during the trial
* Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
* History of or current hypoglycemia as indicated by blood sugar levels of ≤70 mg/dL
* Calcitonin ≥ 50 ng/L
* Triglycerides ≥500 mg/dL
* Untreated cholelithiasis or gallbladder disease
* History of or current angina pectoris, coronary heart disease, congestive heart failure, inflammatory bowel disease, chronic obstructive pulmonary disease, bariatric surgery, pancreatitis, diabetic gastroparesis, or non-arteritic anterior ischemic optic neuropathy
* Liver function test greater than 5 times upper normal limit
* Renal impairment as indicated by eGFR of \<60
* History of hypersensitivity or allergy to tirzepatide
* Pregnant or breastfeeding
* Anticipated to be enrolled in another clinical drug trial during participation in this trial
* Any other reason or clinical condition that the investigators judge may interfere with study participation and/or be unsafe for a participant

Primary outcomes:
measure: Cue-induced Cravings for Alcohol
timeFrame: Baseline visit and 5 weeks after baseline visit.
measure: Incidence and Severity of Adverse Events
timeFrame: Epic monitoring throughout the trial and PRISE administered at study weeks 2-5 (visits 4-7).
Secondary outcomes:
measure: Penn Alcohol Craving Scale (PACS)
timeFrame: At each study visit except for screening up to and including the final visit 5 weeks after baseline.
measure: Monetary Choice Questionnaire (MCQ)
timeFrame: Baseline visit and 5 weeks after baseline visit.
measure: Visual Probe Task
timeFrame: Baseline visit and 5 weeks after baseline visit.
measure: Percent days abstinent
timeFrame: At each study visit except for screening up to and including the final visit 5 weeks after baseline.
measure: Percent heavy drinking days
timeFrame: At each study visit except for screening up to and including the final visit 5 weeks after baseline.
measure: Drinks per drinking day
timeFrame: At each study visit except for screening up to and including the final visit 5 weeks after baseline.
measure: Iowa Gambling Task (IGT)
timeFrame: Baseline visit and 5 weeks after baseline visit.
measure: Clinical Institute Withdrawal Assessment (CIWA)
timeFrame: At each study visit up to and including the final visit 5 weeks after baseline.
measure: Blood Sugar
timeFrame: At each study visit up to and including the final visit 5 weeks after baseline.
measure: Hemoglobin A1c
timeFrame: Baseline and 5 weeks after baseline visit.
measure: Weight
timeFrame: At each study visit up to and including the final visit 5 weeks after baseline.
measure: Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: At each study visit except for screening up to and including the final visit 5 weeks after baseline.
measure: Patient Health Questionnaire-8 (PHQ-8)
timeFrame: At each study visit except for screening up to and including the final visit 5 weeks after baseline.
measure: Generalized Anxiety Disorder-7 (GAD-7)
timeFrame: At each study visit except for screening up to and including the final visit 5 weeks after baseline.
measure: WHO Quality of Life (WHOQOL-BREF)
timeFrame: Baseline and 5 weeks after baseline visit.
measure: Temporal Experience of Pleasure Scale (TEPS)
timeFrame: Baseline and 5 weeks after baseline visit.
measure: Heart rate
timeFrame: At each study visit up to and including the final visit 5 weeks after baseline.
measure: Blood pressure
timeFrame: At each study visit up to and including the final visit 5 weeks after baseline.
measure: Assessment of Blind
timeFrame: 5 weeks after baseline visit.
measure: Stanford Efficacy of Treatment Scale (SETS)
timeFrame: Baseline visit.
measure: Fibrosis-4 (FIB-4)
timeFrame: Screening visit and 5 weeks after baseline visit.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Jamaica Plain
country: United States
facility: Brigham and Women's Faulkner Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Joji Suzuki, MD
role: PRINCIPAL_INVESTIGATOR
References: