The Affiliated Hospital of Hangzhou Normal University
Hangzhou, Zhejiang, 310015, China
NCT Number: NCT07399600
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 opening soon.
Get Notified18 year–65 year
All sexes
Interventional
Not applicable
Hangzhou, Zhejiang, 310015, China
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
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.
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.
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).
Time frame: From baseline to the end of treatment (Week 4)
Time frame: From baseline to mid-treatment (Week 2), end of treatment (Week 4), and at 1-, 3-, and 6-month follow-up
Time frame: From baseline to mid-treatment (Week 2), end of treatment (Week 4), and at 1-, 3-, and 6-month follow-up
Time frame: From baseline to the end of treatment (Week 4)
Time frame: From baseline to the end of treatment (Week 4)
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
G-FCQ-T The General Food Craving Questionnaire-Trait (G-FCQ-T) is a self-reported instrument used to assess the general tendency to experience food cravings. It comprises 21 items. Participants rate each item on a 6-point Likert scale ranging from 1 ("Never") to 6 ("Always"). The total score is the sum of all item ratings, with a possible range from 21 to 126. A higher total score indicates a more severe trait propensity for food craving.
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
G-FCQ-S The General Food Craving Questionnaire-State (G-FCQ-S) is a self-reported instrument used to assess the current, momentary state of food craving. It comprises 15 items. Participants rate each item on a 6-point Likert scale ranging from 1 ("Strongly Disagree") to 6 ("Strongly Agree"). The total score is the sum of all item ratings, with a possible range from 15 to 90. A higher total score indicates a more intense current state of food craving.
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Subjective food craving is assessed using a Visual Analogue Scale (VAS). Participants indicate their current, momentary level of food craving by marking a point on a 100-mm horizontal line. The left endpoint (0 mm) is labeled "No food craving at all," and the right endpoint (100 mm) is labeled "The most intense food craving imaginable." The score is determined by measuring the distance from the left endpoint to the participant's mark, ranging from 0 to 100. A higher score indicates a more intense subjective feeling of food craving.
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
The Alcohol Use Disorders Identification Test (AUDIT) is a simple, self-reported screening tool developed by the World Health Organization (WHO) to identify hazardous and harmful patterns of alcohol consumption. The questionnaire consists of 10 items. The first 8 items are scored on a scale from 0 to 4. Items 9 and 10 are scored 0, 2, or 4. The total score is the sum of all item ratings, with a possible range from 0 to 40. A higher total score indicates a greater likelihood of hazardous and harmful alcohol use, as well as possible alcohol dependence.
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
The Penn Alcohol Craving Scale (PACS) is a self-reported questionnaire designed to measure the intensity of an individual's craving for alcohol over the past week. The scale consists of 5 items assessing the frequency, duration, and intensity of craving, the ability to resist drinking, and the overall rating of craving. Each item is rated on a 6-point scale from 0 to 6, with varying verbal anchors for each item (e.g., "Never" to "Nearly All the Time"). The total score is the sum of all 5 item ratings, with a possible range from 0 to 30. A higher total score indicates a more severe level of subjective alcohol craving.
Time frame: baseline, mid-treatment (Week 2), end of treatment (Week 4), 1, 3, 6 months
Alcohol consumption is assessed using the Timeline Followback (TLFB) method, a structured interview that provides a quantitative estimate of an individual's daily drinking. Using a calendar to aid recall, participants retrospectively report their daily alcohol consumption over a specified period (e.g., the past 30 days). The data is used to calculate key metrics such as the number of drinking days, the number of heavy drinking days, and the average number of standard drinks consumed per day or per week. A higher value indicates a greater level of alcohol consumption.
Time frame: From baseline to mid-treatment (Week 2) and end of treatment (Week 4)
Resting-state functional connectivity (rs-FC) will be assessed using functional magnetic resonance imaging (fMRI). This measures the temporal correlation of spontaneous brain activity between different neural regions, forming functional networks (e.g., Default Mode Network, Executive Control Network). The strength of connectivity is represented by correlation coefficients (z-values). A higher absolute value indicates stronger functional connectivity.
Time frame: From baseline to mid-treatment (Week 2) and end of treatment (Week 4)
The amplitude of low-frequency fluctuations (ALFF) will be calculated from resting-state fMRI data. It measures the intensity of spontaneous neural activity in specific brain regions. The value is typically presented as a normalized Z-score. A higher ALFF value indicates greater regional spontaneous neural activity.
Contact information is provided by the study sponsor or research team.
The Affiliated Hospital of Hangzhou Normal University
Other
Personalized Transcranial Magnetic Stimulation for Metabolic Dysfunction and Alcohol-Related Liver Disease (MetALD): A Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Acronym: P-TMS MetALD
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