This clinical trial aims to test the effectiveness and safety of semaglutide, a GLP-1 receptor agonist, in treating moderate to severe alcohol use disorder (AUD) in Veterans. Participants who qualify will be randomly assigned to receive either semaglutide injections or placebo injections over a 24-week period, followed by a 4-week post-treatment safety assessment period. Participants receiving semaglutide will start with a low dose, gradually increasing to a maximum of 2.4 milligrams (mg) per week, depending on their tolerance. The primary measure of success will be a reduction in risky drinking, assessed through a reliable calendar-based interview method called the Timeline Follow-Back (TLFB), a well-validated calendar-based interview technique for recording daily alcohol consumption. The purpose of this research is to gather information on the safety and effectiveness of semaglutide for treating AUD, potentially offering a new and more appealing treatment option.
Veteran
World Health Organization's (WHO) risk drinking level of Very High or High in the 28 days prior to screening (based on screening TLFB)
Current diagnosis of moderate or severe alcohol use disorder (AUD), i.e., meeting at least 4 of 11 DSM-5 AUD criteria, based on semi-structured diagnostic exam, the Mini-International Neuropsychiatric Interview (MINI)
Able and willing to provide informed consent
Medical History (medical history form)
Type 1 diabetes
History of acute or chronic pancreatitis
History of diabetic ketoacidosis
Parallel
Semaglutide
DrugWeekly subcutaneous injections of semaglutide up to 2.4 milligram (mg)/week or maximum tolerated dose. Initial dosing starting at 0.25 for weeks 1-4. Further titration up to 2.4 mg weekly starting at week 5.
Placebo
DrugWeekly subcutaneous injections of placebo mimicking treatment procedure.
Two-level reduction in the World Health Organization (WHO) risk drinking level assessed in the last 28 days of intervention
Number of participants with at least a two-level reduction, from baseline risk level, in WHO risk drinking level. The WHO risk drinking levels categorize alcohol consumption into four groups: low (level 1; 0-2.86 standard drinks/day for men; 0-1.43 drinks/day for women), moderate (level 2; 2.87-4.29 standard drinks/day for men; 1.44-2.86 drinks/day for women), high (level 3; 4.3-7.14 standard drinks/day for men; 2.87-4.29 drinks/day for women), and very high (level 4; \>7.15 drinks/day for men; \>4.3 drinks/day for women). One standard drink is 14 grams (g) of alcohol or approximately 12oz beer, 5oz wine, or 1.5oz of liquor. A 2-level reduction, such as moving from very high to moderate risk, is considered a significant clinical improvement.
Adverse events of special interest (assessment of safety and tolerability)
Safety and tolerability will be assessed by comparing the proportion of participants experiencing an adverse event of special interest (AESI) in the semaglutide 2.4 mg treatment group versus placebo group.
No heavy drinking days over the last 28 days of intervention
Proportion of subjects with no heavy drinking days. Heavy drinking is defined as \>4 standard drinks in a day for men and \>3 for women. This endpoint will be measured per participant self-report using timeline follow back methods.
Two-level reduction in the World Health Organization (WHO) risk drinking level assessed in the last 56 days of intervention
Number of participants with at least a two-level reduction, from baseline risk level, in WHO risk drinking level. The WHO risk drinking levels categorize alcohol consumption into four groups: low (level 1; 0-2.86 standard drinks/day for men; 0-1.43 drinks/day for women), moderate (level 2; 2.87-4.29 standard drinks/day for men; 1.44-2.86 drinks/day for women), high (level 3; 4.3-7.14 standard drinks/day for men; 2.87-4.29 drinks/day for women), and very high (level 4; \>7.15 drinks/day for men; \>4.3 drinks/day for women). One standard drink is 14 grams (g) of alcohol or approximately 12oz beer, 5oz wine, or 1.5oz of liquor. A 2-level reduction, such as moving from very high to moderate risk, is considered a significant clinical improvement.
Moderation effects of baseline characteristics
Baseline characteristics such as race, age, psychiatric comorbidity, psychiatric treatment, and impulsivity will be assessed for moderation on semaglutide treatment effects on the endpoints of at least a WHO-2LRR and NHDD, which will help to address generalizability of study findings.
Repeated measures assessment of primary and NHDD secondary outcomes
Repeated measures assessment of the primary outcome (proportion of subjects with WHO-2LRR) and a secondary outcome (proportion of subjects with NHDD) for each month over the entirety of the trial.
Clinical Global Impression-Improvement (CGI-I)
CGI-I scale is a clinician-rated tool designed to assess treatment response and the efficacy of interventions in clinical studies of patients with mental disorders including AUD, which assesses how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention with a Likert scale ranging from 1 (very much improved) to 7 (very much worse). The CGI-I will be measured at the end of the ascertainment phase.
Quality of Life (QoL)
Quality of life will be assessed using the Veterans RAND-12 (VR-12), which is a 12-item self-administered instrument used to measure health-related quality of life. The 12 items in the questionnaire correspond to eight principal physical and mental health domains, which are summarized into two scores, a physical health summary measure (PCS-physical component score) and a mental health summary measure (MCS-mental component score). These provide an important contrast between physical and psychological health status. Each VR-12 item response will be coded numerically (e.g., 1-5 or 1-6), then transformed to a score on a 0-100 scale. The transformed PCS score (PCS\_T) and MCS score (MCS\_T) are summations of products of the transformed scores.
Brief Addiction Monitor - Revised (BAM-R)
The BAM-R, a structured instrument of multidimensional clinical outcome monitoring progress in addiction treatment, has three domains of substance use (alcohol and drug use frequency, craving), risk factors (sleep, mood, housing instability, legal issues), and protective factors (recovery supports, abstinence confidence, self-help participation). Each item is scored on a 5-point Likert scale (0-4). The subscore ranges of the three domains are 0-12 for substance use, 0-28 for risk factors, and 0-16 for protective factors. The BAM-R will be self-reported at each visit, and the three subscores will be analyzed for improvements over time by treatment groups.
Click on the lead sponsor to view all of their trials.
