The Safety and Effectiveness of dTMS for Reducing Antipsychotic-induced Weight Gain

N/ANot Yet RecruitingNCT07795554

Second Xiangya Hospital of Central South University60 enrolled

Overview

Antipsychotic-induced metabolic disturbances, especially weight gain, are common in patients with schizophrenia. There are no hitherto effective treatments for reducing antipsychotic-induced weight gain. Recently, research suggest that Accelerated dTMS (a-dTMS) which deliver more than one daily TMS session indicates greater efficacy than other TMS treatment. Symptom provocation is believed to improve the clinical responses to TMS. In this study, the investigators, firstly, evaluate the safety and effectiveness of a-dTMS for reducing antipsychotic-induced weight gain and secondly, to establish a predictive model of therapeutic response and to explore the underlying mechanisms of dTMS for reducing antipsychotic-induced weight gain, based on multimodal radiomics and metabolomics approaches.

The underlying causes of antipsychotic-induced weight gain are still unknown. Some research point out that it has something to do with metabolic disturbances and changes in appetite and food intake, acting food-craving-like behave which some points are similar to addiction. With fMRI study, it is reported having dysfunction between prefrontal and insula cortex of its cognitive regulation, interoceptive signals and reward control. dTMS, H coil in particular, simultaneously targets prefrontal and insula cortex, approved by FDA for Smoking Addiction recently. Previous study has been deconstrued that H coil could significantly improve weight gain than figure-eight Coils. Moreover, It is reckoned that TMS has state-dependent effects on brain circuitry, suspected that symptom provocation may be made it more susceptible to modulation which may improve response. Therefore, this study is to explore the efficacy of a-dTMS on antipsychotic-induced appetite, and use multimodal radiomics and metabolomics approaches to unveil the underlying mechanisms of dTMS for reducing antipsychotic-induced weight gain. With regard to investigate this, we will be carried out a randomized, double-blind, sham-controlled clinical trial. 60 Patients with schizophrenia will be randomly treated with active a-dTMS or sham condition for 3 sections' interventions per day last for 10 days. The follow-ups are at baseline, the 12th day and the 42th day after the end of treatment. The main outcome measures include the change in body weight, BMI, TFEQ score, FCQ-S score, FCQ-T score and the resting and task-state EEG-fMRI imaging data.

Study Type

INTERVENTIONAL

Allocation

Interventions

dTMS of accelerated intermittent theta burst stimulation, ACC-iTBSDEVICE

The intensity of the stimulator is set at 80% of resting motor threshold (RMT), and the other parameters are set to triplet 50Hz bursts, repeat at 5Hz, 2s seconds on and 8 seconds off, 1800 pulses per session, total duration of 9 minutes and 52 seconds.

Sham stimulationDEVICE

The same procedure will be performed in sham coil induced acoustic and scalp sensations similar to those induced by the active coil, but without electromagnetic penetration into the brain and without neural activation.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Aged between 18-60. * Meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for schizophrenia, confirmed by the Structured Clinical Interview for DSM-5 (SCID-5). * Gaining body weight around 7% after intaking antipsychotics within 2 years. * Participants were on a stable medication regimen at the time of enrollment. ●Written informed consent was obtained from both the participants and their legally authorized guardians. Exclusion Criteria: * Participants who switch antipsychotic drugs (APDs) or require a dose modification exceeding 25% of the baseline dosage during the study period. * Diagnosed with other mental diseases in accordance with DSM-V. * Comorbid with other severe physiological diseases. * Active suicidal ideation. * A history of alcohol or substance use disorder (or abuse). * Presence of metal implants or any other conditions contraindicated for magnetic resonance imaging (MRI). * Presence of intracranial metal or electronic devices, a personal or family history of epilepsy, or any other standard contraindications to deep transcranial magnetic stimulation. * Receipt of regular transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), or weight-loss interventions within the past month. * Pregnant or lactating women

Outcomes

Primary Outcomes

Change in BMI

Unit of measure: BMI in kg/m\^2 (weight in kilograms, height in meters)

Time frame: Change in BMI between baseline and the end of the treatment (day 12) and follow-up (day 42)

Change in body weight

Change in body weight (kg) from baseline to Day 12 (end of treatment) and to Day 42 (follow-up), to evaluate the effectiveness of dTMS in reducing antipsychotic-induced weight gain.

Time frame: Change in body weight between baseline and the end of the treatment (day 12) and follow-up (day 42)

Secondary Outcomes

Change in abdominal and hip circumference

The Change in abdominal and hip circumference absolute values (cm) will be measured at baseline and the end of the treatment (day 12) and follow-up (day 42) to evaluate weight-related treatment responses of dTMS.

Time frame: Change in abdominal and hip circumference between baseline and the end of the treatment (day 12) and follow-up (day 42)

Change in Three Factor Eating Questionnaire (TFEQ)

The Food Cravings Questionnaire-Trait (FCQ-T) is a self-reported measures which is a 39-item questionnaire that has nine subscales: intentions and plans to consume food, outcome expectancy of positive reinforcement, outcome expectancy of relief from negative states, anticipated lack of overeating control, preoccupation with food, physiological deficits and responses which may elicit craving, emotions experienced during food craving, external and internal cues that trigger cravings, and guilt.

Time frame: Change in TFEQ between baseline and the end of the treatment (day 12) and follow-up (day 42)

Change in Food Cravings Questionnaire-Trait (FCQ-T)

The change of food craving will be evaluated by Food Cravings Questionnaire-Trait (FCQ-T), a self-report multidimensional questionnaire composed of 39 items aimed to investigate food addiction and eating disorders. Total FCQ-T score will be used as a general measure of trait craving; individual FCQ-T scores related to the 9 measured craving dimensions could be useful in identifying and differentiating craving profiles between specific populations.

Time frame: Change in FCQ-T between baseline and the end of the treatment (day 12) and follow-up (day 42)

Change in Food Craving Questionnaire State (FCQ-S)

The Food Craving Questionnaire-State (FCQ-S) is a 15-item self-report measure to assess momentary, state-dependent food craving. The instrument consists of five multidimensional subscales: (1) intense desire to eat, (2) anticipation of positive reinforcement from eating, (3) anticipation of relief from negative states and feelings as a result of eating, (4) lack of control over eating, and (5) craving as a physiological state. Respondents rate each item on a 5-point Likert scale ranging from 1 ("strongly disagree") to 5 ("strongly agree"). Total scores are calculated by summing all 15 item responses, yielding a possible range of 15 to 75. Higher total scores indicate more intense current state food cravings.

Time frame: Change in FCQ-S between baseline and the end of the treatment (day 12) and follow-up (day 42)

Change of Visual Analogue Scale, VAS

The VAS is a simple, quick-to-administer, and sensitive instrument for detecting acute fluctuations in food craving, hunger, and related motivational states in response to food cue exposure. In the context of food cue reactivity, the VAS is administered immediately before and after presentation of food stimuli (e.g., pictorial food cues, actual food exposure, or virtual reality food environments) to capture acute changes in craving, hunger, appetite, and related motivational states. The VAS consists of a 100-mm horizontal line anchored at each end by verbal descriptors representing the extremes of the construct being measured, typically ranging from 0 ("not at all" or "no desire at all") to 100 ("extremely" or "very strong desire").The score is determined by measuring the distance in millimeters from the left anchor to the respondent's mark, yielding a possible range of 0 to 100, with higher scores indicating greater intensity of the measured construct.

Time frame: Change in VAS between each food cue induced craving and food cue reactivity before and after

Change in parameters of the Stop Signal Task, SST

The SST aims to access cognitive behavioral inhibition control. The study employed a task that comprised randomly interleaved NoGo and Stop-Signal trials to examine both types of inhibition. The study measured six behavioral parameters of interest: namely Mean Go reaction time (GoRT), Stop-Signal mean reaction time (SSRT), Stop-Signal delay (SSD), Target accuracy, Go trial accuracy, and NoGo Accuracy. The primary outcome measure derived from the SST is the stop-signal reaction time (SSRT) , which is an estimated measure of the speed of the inhibitory process. The SSRT is calculated by subtracting the mean or median stop-signal delay (SSD) from the mean or median reaction time on go trials. Higher SSRT values indicate longer inhibition latency and thus poorer inhibitory control, whereas lower SSRT values indicate faster inhibition and better inhibitory control.

Time frame: Change in parameters of SST between baseline and the end of the treatment (day 12) and follow-up (day 42)

Change in parameters of the Go/No-Go Task (GNG)

The Go/No-Go Task (GNG) is a computerized behavioral paradigm that measures response inhibition-specifically, the ability to withhold a prepotent motor response to a frequently occurring stimulus when an infrequent, conflicting stimulus occurs.The GNG task comprises two types of trials presented in random order: Go trials (typically 70-80% of all trials) and No-Go trials (typically 20-30% of all trials).The most critical outcome derived from the GNG task is the No-Go error rate, calculated as the number of incorrect responses on No-Go trials divided by the total number of No-Go trials. Higher No-Go error rates indicate poorer inhibitory control.

Time frame: Change in parameters of GNG between baseline and the end of the treatment (day 12) and follow-up (day 42)

Change in Blood laboratory parameters

About 20ml blood samples were collected intravenously to test blood routine, liver and kidney function, electrolytes and other routine tests. Changes in lipid metabolism will be evaluated by Cholesterol (mg/dL), Triglycerides (mg/dL), High-Density Lipoprotein Cholesterol (mg/dL), Low-Density Lipoprotein Cholesterol (mg/dL), Fasting Blood Glucose (mmol/L).

Time frame: Change in Blood laboratory parameters between baseline and the end of the treatment (day 12) and follow-up (day 42)

Change in correlation of fMRI and EEG functional connectivity

Examines how brain connectivity patterns measured by fMRI (blood-flow activity) relate to connectivity patterns measured by EEG (electrical activity).

Time frame: Change in correlation of fMRI and EEG functional connectivity between baseline and the end of the treatment (day 12) and follow-up (day 42)