The study will compare alcohol use in two groups of subjects. One group will be assigned to the Deep TMS treatment and the other group will be assigned to the sham treatment. This is a prospective, 6-month, double blind, randomized, controlled, multi-center trial in outpatients recruited in both academic and private research centers. The study population will consist of subjects diagnosed with moderate to severe AUD. The study is comprised of three phases:
1. Pre-study Screening and Baseline Phase 2. Acute Treatment Phase and 3. Maintenance Treatment and Follow up Phase
Subjects of all ethnic and gender categories, ages ranging between 18-86 years will be screened for study eligibility according to the inclusion and exclusion criteria. Subjects who meet the eligibility criteria and are willing to sign an informed consent form will be enrolled in the study. The subjects' demographic and baseline characteristics, as well as their overall medical condition will be assessed prior to treatment administration.
Eligible patients will be randomized with a 1:1 ratio to one of two study groups (treatment or sham) and stratified by site. Randomization will be employed to avoid bias in the assignment of subjects to treatment group. All subjects will undergo the same treatment regimen, regardless of the assigned treatment group. The acute treatment phase will include 15 treatment visits over a period of 3-5 weeks.
The Maintenance Treatment \& Follow-up phase will include one treatment visit per week from the end of the Acute Treatment Phase until the 6 month follow-up visit.
At each treatment session, prior to stimulation onset, alcohol related cues will be presented to the subject. After the offset of the alcohol cue presentation, active or sham Deep TMS stimulation will be administered.
The study design is directed towards a comparison between active treatment and sham, up to 4 months and 6 months follow-up. Efficacy will be assessed using the primary efficacy measure of the percent heavy drinking days during months 2, 3 and 4, based on the Time Line Follow Back (TLFB) reporting and supportive PEth results. Additionally, several subject assessment scales will be used during the course of the study to assess alcohol use and alcohol craving.
Safety will be assessed, including monitoring the severity, causality and frequency of all adverse events, vital signs, and physical and neurological examination.
Male or female subjects, 18-86 years old.
Subjects diagnosed with AUD and who meet criteria for moderate (4-5 out of the 12 symptoms) to severe (> 6 out of the 12 symptoms) AUD according to the DSM-5 diagnostic criteria as determined by a licensed clinician according to the DSM-5 criteria, and verified with the Mini International Neuropsychiatric Interview (Standard MINI version 7.0.2).
Subjects who have a history of at least 24 heavy drinking days during the 90 days prior to screening, based on TLFB.
Treatment seeking individuals with a treatment goal of achieving abstinence or reducing heavy drinking.
Subjects diagnosed with schizophrenia or chronic psychotic disorder as determined by a licensed clinician according to the DSM-5 criteria, and verified with the Mini International Neuropsychiatric Interview (Standard MINI version 7.0.2).
Subjects with present suicidal risk as assessed by the investigator or significant suicide risk based on MADRS item 10 score of 4 or 6, or a history of attempted suicide in the last year.
Subjects who initiated treatment with any of the following medications which are known to effect alcohol consumption, within 30 days of the Screening visit: acamprosate, baclofen, buprenorphine, disulfiram, gabapentin, naltrexone, topiramate and varenicline.
Subjects with a significant medical illness that is not well controlled (e.g., hepatic impairment, diabetes, hypertension, heart disease, septicemia, active tuberculosis, progressive neoplasm, frequent and severe migraine headaches, etc.).
Parallel
Deep TMS (DTMS)
DeviceThe Deep TMS group will receive 30 active sessions in 15 visits (i.e., 2 treatments per visit) over a period of 3-5 weeks in the Acute Treatment Phase. In the Maintenance Treatment \& Follow-up phase subjects will receive one treatment session per week from the end of the Acute Treatment Phase until the 6-month follow-up visit. All treatment sessions will consist of 2 treatments per day with a 30 minute interval in between. Each treatment will last approximately 20 minutes.
Sham (No Treatment)
DeviceThe control group will receive 30 Sham sessions in 15 visits (i.e., 2 treatments per visit) over a period of 3-5 weeks in the Acute Treatment Phase. In the Maintenance Treatment \& Follow-up phase subjects will receive one treatment session per week from the end of the Acute Treatment Phase until the 6-month follow-up visit. All treatment sessions will consist of 2 treatments per day with a 30 minute interval in between. The control group will receive inactive/sham treatment with identical parameters to the Deep TMS treatment.
Difference in proportion of patients who attain zero (0) heavy drinking days
The difference in the proportion of patients who attain zero (0) heavy drinking days in the Treatment group versus the Sham control group in months 2, 3 and 4 following initiation of the Acute Phase, based on TLFB reporting and supportive PEth results. Month 1 is considered a "Grace Period" as this is the time during which the full treatment dose of the Acute Phase is being delivered.