iTBS for Increased Appetite Induced by Antipsychotics

Study Overview
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Brief Summary
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Antipsychotics are prone to cause metabolic side effects, including weight gain, hyperglycemia, insulin resistance, hyperlipidemia and so on, leading to a 2-3 times higher risk of death in patients with schizophrenia compared to healthy people. Conventional high-frequency rTMS have been used to treat people with obesity and showed certain effectiveness. However, studies involving schizophrenia patients and intermittent theta burst (iTBS) mode are rarely seen. The goal of this clinical trial is to evaluate the efficacy and safety of iTBS on ameliorating increased appetite induced by antipsychotics in people with schizophrenia.

Detailed Description
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The study will evaluate the efficacy and safety of iTBS on ameliorating increased appetite induced by antipsychotics in people with schizophrenia by measuring changes in clinical ratings at baseline, after all the treatments, and 2 weeks, 4 weeks after intervention. 60 schizophrenia patients will be randomized to receive active or sham interventions administered to the left dorsolateral prefrontal cortex. The experimental group will be applied to active iTBS rTMS involving 600 pulses (3 minutes), 5x daily at 60 minutes intervals for 5 days. Changes in appetite from baseline to the end of the study will be measured by Three Factor Eating Questionnaire (TFEQ), Food Cravings Questionnaire-Trait (FCQ-T), Food Cravings Questionnaire-State (FCQ-S) and Visual Analogue Scale (VAS). Clinical symptoms and mood status will be assessed by Positive and Negative Symptom Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS) and Clinical Global Impression (CGI). Improvement of cognition could be measured by Delay Discounting Task (DDT), Stop-signal task (SST) and MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB). Changes of appetite related Indicators of glycolipid metabolism and neuroregulatory factor, along with microflora before and after intervention will be recorded by collecting blood and feces specimens. The adverse effect will be evaluated by Treatment Emergent Symptom Scale (TESS) and Adverse Event Record Form (AERF). Task-based magnetic resonance imaging (MRI) and arterial spin labeling (ASL) will be used to measure changes of brain activity associated with food stimuli and cerebral blood flow(CBF) before and after treatment.

Official Title
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Effects of Intermittent Theta Burst Stimulation (iTBS) on Increased Appetite Induced by Antipsychotics in Patients With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Device: Active iTBS
* Device: Sham iTBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18-40 years old; Meeting the diagnostic criteria for schizophrenia in DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition); BMI ≥ 25kg/m 2 or over 10% weight gain after taking antipsychotics in the last year; Not receiving TMS therapy in the past month; Using no more than two antipsychotic medications, not using antidepressants, mood stabilizers and other drugs, but allowing short-term use of benzodiazepines, benzhexol and propranolol; Signing written informed consents voluntarily. Exclusion Criteria: Other severe mental illnesses, mental retardation, dementia and severe cognitive impairment according to diagnostic criteria of ICD-10 or DSM-5; Abnormal brain structure or function owing to any major physical disease, neurological disease, traumatic brain injury, etc.; Metallic implants, pacemakers, epilepsy history or other contraindications of TMS; Suicidal thoughts or behaviors; Alcohol or substance abuse; Pregnant or lactating women; Other contraindications of MRI; Receiving regular MECT, or weight-loss therapy in the latest month; Other abnormal examination results considered to be inappropriate for inclusion by researchers.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled clinical trial testing iTBS versus sham
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: active stimulation<br>Intermittent theta burst stimulation to the dorsolateral prefrontal cortex; 5 sessions per day, for 5 days. | Device: Active iTBS<br>* MagPro X100<br>|
| Sham Comparator: Sham stimulation<br>Sham stimulation to the dorsolateral prefrontal cortex; 5 sessions per day, for 5 days. | Device: Sham iTBS<br>* MagPro X100<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in body mass index (BMI) | Weight gain will be assessed by BMI, caculated by weight in kilograms divided by height in meters squared | Baseline, after 5 treatment days, 2 weeks and 4 weeks post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Positive and Negative Symptom Scale (PANSS) | Range from 30 to 210, higher score indicates more severe positive and negative symptoms. | Baseline and 4 weeks post-treatment | 
| Changes in Calgary Depression Scale for Schizophrenia (CDSS) | Range from 0 to 27, higher score indicates more severe affective symptoms. | Baseline and 4 weeks post-treatment | 
| Changes in the Clinical Global Impressions (CGI) | The Clinical Global Impressions (CGI) scale, quantifying the severity of psychopathology, ranging from 1 to 7 and improvements, ranging from 1 to 7 after treatments | Baseline and 4 weeks post-treatment | 
| Changes in the Three-factor Eating Questionnaire (TFEQ) | TFEQ includes three domains, cognitive restraint, uncontrolled eating and emotional eating, range from 21 to 84, higher scores indicates higher appetite. | Everyday from baseline to 4 weeks after treatment | 
| Changes in the Food Cravings Questionnaire-Trait (FCQ-T) | Food Cravings Questionnaire-Trait (FCQ-T) is a six-point Likert scale to measure individuals' stable food craving traits containing nine factors with 39 items. | Everyday from baseline to 4 weeks after treatment | 
| Changes in the Food Cravings Questionnaire-State (FCQ-S) | The Food Cravings Questionnaire-State (FCQ-S) is a five-point Likert scale that measures the intensity of momentary food craving. | Everyday from baseline to 4 weeks after treatment | 
| Changes in the visual analogue scale (VAS) | The visual analogue scale (VAS) will be used to assess the subjective sense of appetite covering hungry, satiety, desire to eat, and overeating, scoring from 0 = not at all to 10 = extremely. | Everyday from baseline to 4 weeks after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, appetite, weight, antipsychotics, iTBS