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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| active stimulation | Active Comparator | Intermittent theta burst stimulation to the dorsolateral prefrontal cortex; 5 sessions per day, for 5 days. |
|
| Sham stimulation | Sham Comparator | Sham stimulation to the dorsolateral prefrontal cortex; 5 sessions per day, for 5 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Active iTBS | Device | Mag-TD |
| |
| Sham iTBS |
| 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 |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Renrong Wu, M.D. Ph.D | Contact | +8615874179855 | wurenrong@csu.edu.cn | |
| Jing Huang, M.D. Ph.D | Contact | 15874290980 | jinghuangserena@csu.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Renrong Wu, M.D. Ph.D | Department of Psychiatry, The Second Xiangya Hospital of Central South University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Central South University | Not yet recruiting | Changsha | Hunan | 410000 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40204331 | Derived | Qin Y, Yang J, Xu B, Yang J, Chen H, Zou T, Teng Z, Liu J, Zhang T, Su Y, Wu R, Dong Z, Yang C, Huang J. Effects of intermittent theta burst stimulation (iTBS) on appetite change and body weight in inpatients with schizophrenia in China: study protocol for a randomised controlled trial. BMJ Open. 2025 Apr 8;15(4):e090932. doi: 10.1136/bmjopen-2024-090932. |
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Data Sharing Plan The proposed study will involve a small sample (60 patients with schizophrenia) recruited from clinical institutions of the Second People's Hospital of Dali Bai Autonomous Prefecture and the Second Xiangya Hospital of Central South University in China. The final dataset will comprise self-reported demographic and clinical characteristics, behavioral and neuroimaging data, along with laboratory data from blood and stool specimens provided by the participants. Because schizophrenia is a reportable severe mental disorder, identifying information will be collected. Although the final dataset is deidentified before it is released for sharing, we believe it is still possible to infer the disclosure of subjects with psychotic characteristics. Patients with schizophrenia belong to a vulnerable group, often accompanied by a sense of stigma. Given the social distress of the participants and the relatively limited area in which we recruited the participants, we thought it would
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D001835 | Body Weight |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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Randomized controlled clinical trial testing iTBS versus sham
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| Device |
Mag-TD |
|
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 brain perfusion. | The arterial spin labeling (ASL) pulse sequences to quantify the cerebral blood flow (CBF). | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in brain function. | Functional MRI (fMRI) based on the blood oxygen level dependent (BOLD) contrast that can detect changes in blood oxygenation to analyze the change of brain function after intervention. | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in MCCB | The MATRICS™ Consensus Cognitive Battery | Baseline and 4 weeks post-treatment |
| Changes in SST. | Stop-signal task (SST) will be used to assess cognitive control. | Baseline, after 5 treatment days, 2 weeks and 4 weeks post-treatment |
| Changes in DDT. | Delay Discounting Task (DDT) will be used to assess impulsiveness in decision making. | Baseline, after 5 treatment days, 2 weeks 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. | Baseline, after 5 treatment days, 2 weeks and 4 weeks post-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. | Baseline, after 5 treatment days, 2 weeks and 4 weeks post-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. | Baseline, after 5 treatment days, 2 weeks and 4 weeks post-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 |
| Changes in the types of intestinal flora. | Feces will be collected and DNA will be extraced for quantitative analysis of intestinal flora composition. | Baseline and 4 weeks post-treatment |
| Changes in plasma agouti related regulatory proteins. | in ng/mL. | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in plasma serum proopioid-melanocortin. | in ng/mL. | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in plasma serum ghrelin. | in ng/mL | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in plasma serum leptin. | in ng/mL. | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in the proportion of of intestinal flora. | Feces will be collected and DNA will be extraced for quantitative analysis of intestinal flora composition. | Baseline and 4 weeks post-treatment |
| Changes in plasma prolactin. | in mcg/L. | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in serum total bile acids. | in mmol/l. | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in glycosylated hemoglobin. | in mmol/mol. | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in serum Low-density lipoprotein cholesterol. | in mg/dl. | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in serum high-density lipoprotein cholesterol. | in mg/dl. | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in serum total cholesterol. | in mg/dl. | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in serum triglycerides. | in mmol/l. | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in serum glucagon-like peptide-1. | in pmol/l. | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in serum glucagon. | in ng/l. | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in serum fasting insulin. | in mmol/l. | Baseline, after 5 treatment days and 4 weeks post-treatment |
| Changes in serum fasting blood glucose. | in mmol/l. | Baseline, after 5 treatment days and 4 weeks post-treatment |
| The Second People's Hospital of Dali Bai Autonomous Prefecture | Recruiting | Dali | Yunnan | 671014 | China |
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