Schizophrenia
Conditions
Keywords
Schizophrenia, appetite, weight, antipsychotics, iTBS
Brief summary
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
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.
Interventions
DEVICEActive iTBS
Mag-TD
DEVICESham iTBS
Mag-TD
Sponsors
Central South University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized controlled clinical trial testing iTBS versus sham
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
1. Age between 18-40 years old; 2. Meeting the diagnostic criteria for schizophrenia in DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition); 3. BMI ≥ 25kg/m 2 or over 10% weight gain after taking antipsychotics in the last year; 4. Not receiving TMS therapy in the past month; 5. Using no more than two antipsychotic medications (including olanzapine, haloperidol, amisulpride, asenapine, risperidone, paliperidone, clozapine, quetiapine, iloperidone, chlorpromazine, sertindole, zotepine), not using antidepressants, mood stabilizers and other drugs, but allowing short-term use of benzodiazepines, benzhexol and propranolol; 6. Signing written informed consents voluntarily.
Exclusion criteria
1. Other severe mental illnesses, mental retardation, dementia and severe cognitive impairment according to diagnostic criteria of ICD-10 or DSM-5; 2. Abnormal brain structure or function owing to any major physical disease, neurological disease, traumatic brain injury, etc.; 3. Metallic implants, pacemakers, epilepsy history or other contraindications of TMS; 4. Suicidal thoughts or behaviors; 5. Alcohol or substance abuse; 6. Pregnant or lactating women; 7. Other contraindications of MRI; 8. Receiving regular MECT, or weight-loss therapy in the latest month; 9. Other abnormal examination results considered to be inappropriate for inclusion by researchers.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in body mass index (BMI) | Baseline, after 5 treatment days, 2 weeks and 4 weeks post-treatment | Weight gain will be assessed by BMI, caculated by weight in kilograms divided by height in meters squared |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in serum fasting blood glucose. | Baseline, after 5 treatment days and 4 weeks post-treatment | in mmol/l. |
| Changes in Positive and Negative Symptom Scale (PANSS) | Baseline and 4 weeks post-treatment | Range from 30 to 210, higher score indicates more severe positive and negative symptoms. |
| Changes in Calgary Depression Scale for Schizophrenia (CDSS) | Baseline and 4 weeks post-treatment | Range from 0 to 27, higher score indicates more severe affective symptoms. |
| Changes in the Clinical Global Impressions (CGI) | Baseline and 4 weeks post-treatment | 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 |
| Changes in brain perfusion. | Baseline, after 5 treatment days and 4 weeks post-treatment | The arterial spin labeling (ASL) pulse sequences to quantify the cerebral blood flow (CBF). |
| Changes in brain function. | Baseline, after 5 treatment days and 4 weeks post-treatment | 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. |
| Changes in MCCB | Baseline and 4 weeks post-treatment | The MATRICS™ Consensus Cognitive Battery |
| Changes in SST. | Baseline, after 5 treatment days, 2 weeks and 4 weeks post-treatment | Stop-signal task (SST) will be used to assess cognitive control. |
| Changes in DDT. | Baseline, after 5 treatment days, 2 weeks and 4 weeks post-treatment | Delay Discounting Task (DDT) will be used to assess impulsiveness in decision making. |
| Changes in the Three-factor Eating Questionnaire (TFEQ) | Baseline, after 5 treatment days, 2 weeks and 4 weeks post-treatment | TFEQ includes three domains, cognitive restraint, uncontrolled eating and emotional eating, range from 21 to 84, higher scores indicates higher appetite. |
| Changes in the Food Cravings Questionnaire-Trait (FCQ-T) | Baseline, after 5 treatment days, 2 weeks and 4 weeks post-treatment | 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. |
| Changes in the Food Cravings Questionnaire-State (FCQ-S) | Baseline, after 5 treatment days, 2 weeks and 4 weeks post-treatment | The Food Cravings Questionnaire-State (FCQ-S) is a five-point Likert scale that measures the intensity of momentary food craving. |
| Changes in the visual analogue scale (VAS) | Everyday from baseline to 4 weeks after treatment | 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. |
| Changes in the types of intestinal flora. | Baseline and 4 weeks post-treatment | Feces will be collected and DNA will be extraced for quantitative analysis of intestinal flora composition. |
| Changes in serum fasting insulin. | Baseline, after 5 treatment days and 4 weeks post-treatment | in mmol/l. |
| Changes in plasma agouti related regulatory proteins. | Baseline, after 5 treatment days and 4 weeks post-treatment | in ng/mL. |
| Changes in plasma serum proopioid-melanocortin. | Baseline, after 5 treatment days and 4 weeks post-treatment | in ng/mL. |
| Changes in plasma serum ghrelin. | Baseline, after 5 treatment days and 4 weeks post-treatment | in ng/mL |
| Changes in plasma serum leptin. | Baseline, after 5 treatment days and 4 weeks post-treatment | in ng/mL. |
| Changes in the proportion of of intestinal flora. | Baseline and 4 weeks post-treatment | Feces will be collected and DNA will be extraced for quantitative analysis of intestinal flora composition. |
| Changes in plasma prolactin. | Baseline, after 5 treatment days and 4 weeks post-treatment | in mcg/L. |
| Changes in serum total bile acids. | Baseline, after 5 treatment days and 4 weeks post-treatment | in mmol/l. |
| Changes in glycosylated hemoglobin. | Baseline, after 5 treatment days and 4 weeks post-treatment | in mmol/mol. |
| Changes in serum glucagon-like peptide-1. | Baseline, after 5 treatment days and 4 weeks post-treatment | in pmol/l. |
| Changes in serum glucagon. | Baseline, after 5 treatment days and 4 weeks post-treatment | in ng/l. |
| Changes in serum Low-density lipoprotein cholesterol. | Baseline, after 5 treatment days and 4 weeks post-treatment | in mg/dl. |
| Changes in serum high-density lipoprotein cholesterol. | Baseline, after 5 treatment days and 4 weeks post-treatment | in mg/dl. |
| Changes in serum total cholesterol. | Baseline, after 5 treatment days and 4 weeks post-treatment | in mg/dl. |
| Changes in serum triglycerides. | Baseline, after 5 treatment days and 4 weeks post-treatment | in mmol/l. |
Countries
China
Contacts
Primary ContactRenrong Wu, M.D. Ph.D
Backup ContactJing Huang, M.D. Ph.D
Outcome results
None listed