Antipsychotic Induced Weight Gain, Schizophrenia
Conditions
Keywords
Schizophrenia, Antipsychotic induced weight gain, dTMS
Brief summary
Antipsychotic-induced metabolic disturbances, especially weight gain, are common in patients with schizophrenia. Furthermore, it is reported significant changes in food intake happened in patients with weight gain after intaking antipsychotics. There are no hitherto effective treatments for reducing antipsychotic-induced weight gain. dTMS which is a safe and non-invasive physical treatment indicates greater efficacy than other transcranial magnetic stimulation (TMS) by some research. Apart from that, symptom provocation is believed to improve the clinical responses to TMS. In this study, the investigators, firstly, evaluate the safety and effectiveness of dTMS for reducing antipsychotic-induced weight gain and secondly, unveil whether symptom provocation can affect the clinical responses to TMS.
Detailed description
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. With fMRI study, it is reported having dysfunction between prefrontal and insula cortex of its cognitive regulation, interoceptive signals and reward control. dTMS, H4 coil in particular, simultaneously targets prefrontal and insula cortex. Previous study has been deconstrued that dTMS could significantly improve weight gain. 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 dTMS on antipsychotic-induced appetite, and whether provoking symptoms can improve dTMS clinical responses. With regard to investigate this, the investigators will be carried out a randomized single session dTMS, crossover, sham controlled clinical trial. 30 Patients with schizophrenia will be randomly treated with dTMS after food cue induced craving (FCC), dTMS without FCC and sham condition without FCC. Each session has three days intervals for washout. The follow-ups are at the baseline and after each session immediately. The main outcome measures include the change in Food-Cravings Questionnaires state (FCQ-S) score, Visual Analogue Scale (VAS) score, changes in Stop-Signal test (SST) behavioral assessment and the resting-state functional magnetic resonance imaging data.
Interventions
The study will utilize the H4 coil to administer active Deep Transcranial Magnetic Stimulation (dTMS) to the bilateral insula and prefrontal cortex by Intermittent theta burst stimulation (iTBS). The stimulation intensity is set at 90% 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.
The study will utilize an identical protocol using the H4 coil to administer a sham condition.
Sponsors
Second Xiangya Hospital of Central South University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
This study used a single-blind design, with participants blinded to treatment allocation. The device operator was not blinded due to differing parameter settings between active and sham stimulation, but was not involved in recruitment, clinical assessment, or data analysis. To maintain blinding integrity, participants were prohibited from discussing treatment-related sensations with the operator or among themselves. The sham procedure mimicked the initial scalp sensation of active stimulation to enhance blinding credibility.
Intervention model description
There will be carried out a randomized single session dTMS, crossover, sham controlled clinical trial. 30 Patients with schizophrenia will be randomly treated with dTMS after food cue induced craving (FCC), dTMS without FCC and sham condition without FCC. Each session has three days intervals for washout.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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 repetitive transcranial magnetic stimulation (rTMS), electroconvulsive therapy (ECT), or weight-loss interventions within the past month * Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Food Craving Questionnaire State, FCQ-S | Baseline (Day 1); immediately before and immediately after (within 30 minutes post-session) each daily dTMS session (Day 1, 5 and 9) | The assessment of food cravings. The FCQs consists of 15 items to be scored on a 5-point scale ranging from strongly disagree to strongly agree. Its original form comprises five subscales measuring current food craving in relation to (1) an intense desire to eat, (2) anticipation of positive reinforcement, (3) relief from negative states, (4) lack of control over eating, and (5) hunger. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analogue Scale, VAS | Assessed at three time points (pre-provocation, immediately post-provocation [within 5 min], and immediately post-dTMS [within 30 min]) on Study Days 1, 5, and 9. | The Visual Analogue Scales required the subjects to rate hunger, satiety, thirst, fullness and emptiness on a 0-100 mm scale. The Visual Analogue Scales of Craving was assessed two times: before the provocation procedure, and after the provocation procedure |
| Changes of Stop-Signal mean reaction time (SSRT) | Baseline (Day 1); immediately before and immediately after (within 30 minutes post-session) each daily dTMS session (Day 1, 5 and 9) | 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 SST main outcome is the changes of Stop-Signal mean reaction time (SSRT) |
| Resting-state functional magnetic resonance imaging | Baseline (Day 1); immediately before and immediately after (within 30 minutes post-session) each daily dTMS session (Day 1, 5 and 9) | All patients undergo head MRI scans in Philips Achieva 3.0 T scanner and SIEMENS Prisma 3.0 T scanner. |
| Task-state functional magnetic resonance imaging | Baseline (Day 1); immediately before and immediately after (within 30 minutes post-session) each daily dTMS session (Day 1, 5 and 9) | Measure of the immediate activation (blood-oxygen-level-dependent change) in the brain regions related to appetite neural circuits under food cue reactivity task |
Countries
China
Contacts
CONTACTPing Shao
CONTACTRenrong Wu
Outcome results
None listed