NCT07399600

Brief Summary

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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
105

participants targeted

Target at P50-P75 for not_applicable

Timeline
20mo left

Started Feb 2026

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress14%
Feb 2026Dec 2027

First Submitted

Initial submission to the registry

November 17, 2025

Completed
3 months until next milestone

Study Start

First participant enrolled

February 1, 2026

Completed
9 days until next milestone

First Posted

Study publicly available on registry

February 10, 2026

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2027

Expected
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2027

Last Updated

February 10, 2026

Status Verified

January 1, 2026

Enrollment Period

1.6 years

First QC Date

November 17, 2025

Last Update Submit

February 3, 2026

Conditions

Keywords

Liver Diseases, AlcoholicFatty LiverMetabolic SyndromeTranscranial Magnetic StimulationRandomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

  • Percent Change in Liver Fat Content (LFC) From Baseline to End of Treatment as Measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)

    From baseline to the end of treatment (Week 4)

Secondary Outcomes (29)

  • Change in Controlled Attenuation Parameter (CAP, dB/m) From Baseline as Assessed by Vibration-Controlled Transient Elastography (FibroScan® VCTE)

    From baseline to mid-treatment (Week 2), end of treatment (Week 4), and at 1-, 3-, and 6-month follow-up

  • Change in Liver Stiffness Measurement (LSM, kPa) From Baseline as Assessed by FibroScan® VCTE

    From baseline to mid-treatment (Week 2), end of treatment (Week 4), and at 1-, 3-, and 6-month follow-up

  • LFC From Baseline as Measured by MRI-PDFF

    From baseline to the end of treatment (Week 4)

  • Proportion of Participants Achieving ≥30% or ≥50% Reduction in LFC From Baseline

    From baseline to the end of treatment (Week 4)

  • Change in Serum Levels of Liver Enzymes (ALT, AST, ALP, GGT [U/L]) From Baseline

    baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months

  • +24 more secondary outcomes

Other Outcomes (2)

  • Resting-State Functional Connectivity (rs-FC) Measured by fMRI

    From baseline to mid-treatment (Week 2) and end of treatment (Week 4)

  • Amplitude of Low-Frequency Fluctuations (ALFF) Measured by fMRI

    From baseline to mid-treatment (Week 2) and end of treatment (Week 4)

Study Arms (3)

Conventional rTMS

ACTIVE COMPARATOR
Device: Conventional rTMS

Sham rTMS

SHAM COMPARATOR
Device: Transcranial Magnetic Stimulation Sham

Active rTMS

EXPERIMENTAL
Device: Individually Targeted rTMS

Interventions

Participants will receive individualized transcranial magnetic stimulation (TMS) based on neuroimaging-guided localization of the nucleus accumbens (NAc). After the first MRI scan, participants will be randomized by an independent researcher responsible for data analysis. The individualized stimulation coordinates will be provided to the TMS operator before treatment. Intervention will be delivered using intermittent theta-burst stimulation (iTBS): the coil will be placed tangentially to the scalp over the individualized target. Stimulation parameters: 90% resting motor threshold (RMT); bursts of 3 pulses at 50 Hz; bursts repeated at 5 Hz; a total of 1800 pulses per session; stimulation duration 570 seconds. Each participant will receive 20 sessions in total, with at least 2 treatment days per week (2 sessions/day, 4 sessions/week). MRI and clinical assessments will be repeated at mid-treatment and after treatment completion, with follow-up clinical evaluations at 1, 3, and 6 months.

Active rTMS

Conventional rTMS is applied to the left dorsolateral prefrontal cortex (DLPFC) using the standard 5 cm rule for scalp-based localization. Stimulation is delivered with intermittent theta-burst stimulation (iTBS) at 90% resting motor threshold (RMT), 3 pulses at 50 Hz per burst, repeated at 5 Hz, for a total of 1800 pulses per session. Each session lasts about 570 seconds. Participants complete 20 sessions over 4 weeks, with 2 sessions per day on 2 days per week.

Conventional rTMS

Sham rTMS is delivered using a sham coil or low-intensity stimulation (10% RMT) to mimic the clicking sounds and scalp sensations of active rTMS without producing cortical activation. The sham sessions are matched to the active treatment in frequency, duration, and total number: 20 sessions in 4 weeks (2 sessions/day, 2 days/week, 570 seconds per session).

Sham rTMS

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Affiliated Hospital of Hangzhou Normal University

Hangzhou, Zhejiang, 310015, China

Location

MeSH Terms

Conditions

Liver Diseases, AlcoholicFatty LiverMetabolic Syndrome

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesAlcohol-Induced DisordersAlcohol-Related DisordersSubstance-Related DisordersChemically-Induced DisordersInsulin ResistanceHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 17, 2025

First Posted

February 10, 2026

Study Start

February 1, 2026

Primary Completion (Estimated)

August 31, 2027

Study Completion (Estimated)

December 31, 2027

Last Updated

February 10, 2026

Record last verified: 2026-01

Locations