Clinical trial NCT05783063: iTBS for Increased Appetite Induced by Antipsychotics
Official title: Effects of Intermittent Theta Burst Stimulation (iTBS) on Increased Appetite Induced by Antipsychotics in Patients With Schizophrenia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Schizophrenia
Keywords: Schizophrenia
appetite
weight
antipsychotics
iTBS
Lead sponsor: Central South University
Sponsor class: OTHER
First posted: 2023-03-24
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled clinical trial testing iTBS versus sham
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in body mass index (BMI)
timeFrame: Baseline, after 5 treatment days, 2 weeks and 4 weeks post-treatment
Secondary outcomes:
measure: Changes in Positive and Negative Symptom Scale (PANSS)
timeFrame: Baseline and 4 weeks post-treatment
measure: Changes in Calgary Depression Scale for Schizophrenia (CDSS)
timeFrame: Baseline and 4 weeks post-treatment
measure: Changes in the Clinical Global Impressions (CGI)
timeFrame: Baseline and 4 weeks post-treatment
measure: Changes in brain perfusion.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in brain function.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in MCCB
timeFrame: Baseline and 4 weeks post-treatment
measure: Changes in SST.
timeFrame: Baseline, after 5 treatment days, 2 weeks and 4 weeks post-treatment
measure: Changes in DDT.
timeFrame: Baseline, after 5 treatment days, 2 weeks and 4 weeks post-treatment
measure: Changes in the Three-factor Eating Questionnaire (TFEQ)
timeFrame: Baseline, after 5 treatment days, 2 weeks and 4 weeks post-treatment
measure: Changes in the Food Cravings Questionnaire-Trait (FCQ-T)
timeFrame: Baseline, after 5 treatment days, 2 weeks and 4 weeks post-treatment
measure: Changes in the Food Cravings Questionnaire-State (FCQ-S)
timeFrame: Baseline, after 5 treatment days, 2 weeks and 4 weeks post-treatment
measure: Changes in the visual analogue scale (VAS)
timeFrame: Everyday from baseline to 4 weeks after treatment
measure: Changes in the types of intestinal flora.
timeFrame: Baseline and 4 weeks post-treatment
measure: Changes in plasma agouti related regulatory proteins.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in plasma serum proopioid-melanocortin.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in plasma serum ghrelin.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in plasma serum leptin.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in the proportion of of intestinal flora.
timeFrame: Baseline and 4 weeks post-treatment
measure: Changes in plasma prolactin.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in serum total bile acids.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in glycosylated hemoglobin.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in serum Low-density lipoprotein cholesterol.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in serum high-density lipoprotein cholesterol.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in serum total cholesterol.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in serum triglycerides.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in serum glucagon-like peptide-1.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in serum glucagon.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in serum fasting insulin.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
measure: Changes in serum fasting blood glucose.
timeFrame: Baseline, after 5 treatment days and 4 weeks post-treatment
Other outcomes:
Locations:
city: Changsha
country: China
facility: Central South University
state: Hunan
city: Dali
country: China
facility: The Second People's Hospital of Dali Bai Autonomous Prefecture
state: Yunnan
Study officials:
affiliation: Department of Psychiatry, The Second Xiangya Hospital of Central South University
name: Renrong Wu, M.D. Ph.D
role: PRINCIPAL_INVESTIGATOR
References: