Personalized Transcranial Magnetic Stimulation (TMS) for Metabolic Dysfunction and Alcohol-Related Liver Disease

Personalized Transcranial Magnetic Stimulation for Metabolic Dysfunction and Alcohol-Related Liver Disease (MetALD): A Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial

The goal of this clinical trial is to learn if repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive brain stimulation technique, works to treat Metabolic dysfunction-associated and alcohol-associated liver disease (MetALD). The main questions it aims to answer are:

• Can rTMS effectively treat MetALD?
• Is an individualized, precision-targeted rTMS approach more effective than the standard rTMS method?
• What changes in brain activity are associated with the treatment?

Researchers will compare three different types of stimulation:

• Group A: Individualized rTMS targeting a deep brain reward area (the Nucleus Accumbens) based on each participant's brain scan (fMRI).
• Group B: Standard rTMS applied using the traditional "5 cm" rule for positioning.
• Group C: Sham (placebo) rTMS, which mimics the procedure but delivers no significant magnetic stimulation.

Participants will:

• Be randomly assigned to one of the three groups (A, B, or C).
• Undergo an MRI brain scan before starting treatment.
• Receive a total of 20 rTMS sessions, completing at least 4 sessions per week.
• Have additional MRI scans and clinical assessments halfway through and immediately after the treatment course.
• Attend follow-up visits at 1, 3, and 6 months after treatment completion to assess long-term effects.

Inclusion Criteria:

• Participants are able to understand the study protocol, requirements, and restrictions, are fully informed of potential adverse events, are willing to comply with follow-up visits, and voluntarily sign the informed consent form before enrollment.
• Meet the diagnostic criteria for MASLD according to the Guidelines for the Prevention and Treatment of Metabolic (Non-Alcoholic) Fatty Liver Disease (2024 Edition), and fulfill the European definition of MetALD with moderate alcohol consumption (20-50 g/day for women; 30-60 g/day for men).
• Age between 18 and 65 years.
• Body mass index (BMI) > 24 kg/m².
• No history of alcohol abuse.

Exclusion Criteria:

• Contraindications to magnetic resonance imaging (MRI) or transcranial magnetic stimulation (TMS).
• Mild cognitive impairment, defined as Montreal Cognitive Assessment (MoCA) score < 25.
• Severe comorbid somatic diseases or neurological disorders.
• History of psychiatric disorders, or current use of antipsychotic medications.
• Pregnant or breastfeeding women, or those planning pregnancy.
• Previous TMS treatment within the last 3 months.