Modulation of Repetitive Transcranial Magnetic Stimulation on Hippocampal Neurogenesis and Functional Network in Patients With Schizophrenia

Sponsor

Shanghai Mental Health Center (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT03608462

Collaborator

Shanghai Jiao Tong University School of Medicine (Other)

180

Enrollment

Location

Arms

Anticipated Duration (Months)

5.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Based on the hypothesis that high-frequency repetitive transcranial magnetic stimulation(rTMS) on the right dorsolateral prefrontal cortex(DLPFC) and left parietal cortex(LPC) could normalise cognitive abnormalities by promoting hippocampal neurogenesis and cortical-hippocampal function in patients with schizophrenia,this research plan to utilise multimodal functional magnetic imaging method(including structural MRI,resting-state functional magnetic resonance imaging and 1H-MRS) to investigate therapeutic efficacy of intermittent theta burst stimulation (iTBS) on cognitive impairment in SZ patients with memory defects,as well as to elucidate the correlation between treatment effects and hippocampal neuroplasticity.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Device: repetitive transcranial magnetic stimulation(DLPFC) Device: repetitive transcranial magnetic stimulation(LPC)	N/A

Detailed Description

This study includes 150 schizophrenia patients and 30 healthy controls.This study will investigate 1).abnormalities of hippocampal neurogenesis in patients with schizophrenia compared to healthy controls by using 1H-MRS technique 2a).potential modulation effects of repetitive transcranial magnetic stimulation(rTMS) on hippocampal neurogenesis and cortical-hippocampal function of patients with schizophrenia 2b).the optimal rTMS therapy pattern on promoting hippocampal neurogenesis and improving cortico-hippocampal function by comparing the outcome of stimulating two regions(right dorsolateral prefrontal cortex or left parietal cortex) respectively 3).the therapeutic efficacy of rTMS on cognitive impairments and other psychotic symptoms of patients with schizophrenia by adopting cognitive function and psychotic symptoms evaluation,as well as to explore the optimal rTMS treatment pattern on cognitive function by comparing the outcome of stimulating two regions(DLPFC or LPC) respectively 4)association between therapeutic efficacy of rTMS on cognitive deficits and rTMS modulation on hippocampal neurogenesis and its network function,in order to elucidate the underlying mechanism of therapeutic effects of rTMS on cognitive dysfunction in schizophrenia.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

In this research,we combine a cross-sectional case control study and a randomized controlled study.In this research,we combine a cross-sectional case control study and a randomized controlled study.

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Modulation of rTMS on Hippocampal Neurogenesis and Functional Network in Early Schizophrenia

Actual Study Start Date :

Apr 1, 2019

Actual Primary Completion Date :

Dec 31, 2020

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: rTMS targeting the right DLPFC 60 patients will be randomly allocated into this group,half of them will receive iTBS on the right DLPFC,while the other half will receive sham stimulation.	Device: repetitive transcranial magnetic stimulation(DLPFC) high frequency(20Hz) repetitive transcranial magnetic stimulation on dorsolateral prefrontal cortex(DLPFC) .Duration:10 days.
Sham Comparator: rTMS targeting the left LPC 60 patients will be randomly allocated into this group,half of them will receive iTBS on left LPC,while the other half will receive sham stimulation.	Device: repetitive transcranial magnetic stimulation(LPC) high frequency(20Hz) repetitive transcranial magnetic stimulation on left parietal cortex(LPC).Duration:10 days
No Intervention: Observation group To investigate the abnormalities of hippocampal neurogenesis in patients with early schizophrenia(n=30) compared to healthy controls(n=30)

Arm

Intervention/Treatment

Sham Comparator: rTMS targeting the right DLPFC

60 patients will be randomly allocated into this group,half of them will receive iTBS on the right DLPFC,while the other half will receive sham stimulation.

Device: repetitive transcranial magnetic stimulation(DLPFC)

high frequency(20Hz) repetitive transcranial magnetic stimulation on dorsolateral prefrontal cortex(DLPFC) .Duration:10 days.

Sham Comparator: rTMS targeting the left LPC

60 patients will be randomly allocated into this group,half of them will receive iTBS on left LPC,while the other half will receive sham stimulation.

Device: repetitive transcranial magnetic stimulation(LPC)

high frequency(20Hz) repetitive transcranial magnetic stimulation on left parietal cortex(LPC).Duration:10 days

No Intervention: Observation group

To investigate the abnormalities of hippocampal neurogenesis in patients with early schizophrenia(n=30) compared to healthy controls(n=30)

Outcome Measures

Primary Outcome Measures

Change from baseline in MATRICS Consensus Cognitive Battery [baseline,24 hours after the rTMS treatment,30 days]
MATRICS Consensus Cognitive Battery
Change of hippocampal neurogenesis(from baseline) [baseline,24 hours after the rTMS treatment]
Quantify neural stem cells in hippocampal by using H1-MRS
Change of cortical-hippocampal functional network(from baseline) [baseline,24 hours after the rTMS treatment]
Resting-state fMRI data are acquired
Change from baseline in associative memory [baseline,24 hours after the rTMS treatment,30 days]
associative memory

Secondary Outcome Measures

Change from baseline in Positive and Negative Syndrome Scale(PANSS) [baseline,24 hours after the rTMS treatment,30 days]
Positive and Negative Syndrome Scale(PANSS)
Change from baseline in the Scale for the Assessment of Negative Symptoms(SANS) [baseline,24 hours after the rTMS treatment,30 days]
Scale for the Assessment of Negative Symptoms
Change from baseline in UCSD Performance-based Skills Assessment-Brief(UPSA-B) [baseline,24 hours after the rTMS treatment,30 days]
UCSD Performance-based Skills Assessment-Brief

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Early schizophrenia group:

Inclusion Criteria:

The Structured Interview for Prodromal Symptoms (SIPS) was employed.
Meet the diagnostic criteria of Diagnostic and Statistical Manual Diploma in Social Medicine(DSM-V) schizophrenia or schizophreniform psychosis.
18-50years of age,right-handed,normal vision or corrected vision, Han nationality.
Disease course less than 5 years.
Written informed consent

Observation group: First-episode, In addition to criteria1-3,5,antipsychotics naïve,or antipsychotics withdrawal for more than 3 months.

Intervention group:In addition to criteria 1-6,currently under medication and medically stable for at least 1 month(PANSS score fluctuation<10%);continue the original antipsychotics for at least 1 months after recruitment,with consent of the patients,their psychiatrists and family members.

Exclusion criteria:

Current or past neurological illness,severe physical illness,substance abuse or addiction,alcohol dependence,mental retardation,pregnancy or lactation,extreme agitation, stupor, negative suicide,or those who can not cooperate.A history of MECT within 6 months,or those with contraindications to MRI,rTMS.Medically unstable for at least 1 month (PANSS score fluctuation>10%)

Healthy controls:

Inclusion Criteria:

The Structured Interview for Prodromal Symptoms (SIPS) was employed
Matched to the early schizophrenia group in terms of age,sex ratio,handedness,and estimated premorbid IQ
normal vision or corrected vision, Han nationality
Written informed consent

Exclusion Criteria:

History of psychiatric disease in the subjects themselves or a family history of mental disorder in their first-degree relatives,neurological illness,severe physical illness,substance abuse or alcohol dependence,mental retardation.