Repetitive Transcranial Magnetic Stimulation in Early Psychosis and The Functional Connectivity Biotypes

NCT ID: NCT04853485

Last Updated: 2023-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-01

Study Completion Date

2024-12-31

Brief Summary

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The present study plans to explore different cortical targets of repetitive transcranial magnetic stimulation (rTMS) for populations at the early phase of psychosis, including those at clinical high risk of psychosis and in the first episode of psychosis. The clinical augmentation efficacy will be associated with the brain functional connectivity of these populations.

Detailed Description

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Schizophrenia is a life long illness, the management of its early stage is the key in its long term outcomes. The early stage of schizophrenia includes the prodromal and first episode, during which the patients present psychotic symptoms (positive symptoms, negative symptoms) and cognition deficits. Antipsychotics are often prescribed to treat these symptoms, but more than one third patients do not respond well. Regarding cognition deficits, for example, while the visual spatial learning evaluated using Brief Visuospatial Memory Test-Revised (BVMT-R) of The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) may play an important role in the conversion of psychosis in the prodromal phase, there is still no corresponding intervention.

Repetitive transcranial magnetic stimulation (rTMS) is a new non-invasive brain stimulation. In previous studies, its applications mainly focus on negative symptoms and demonstrate promising findings. However, its efficacy has much needing improvement, urgently needing target optimizing and precision, especially according to the prominent complaints of patients. To solve this issue, the present project proposed to make efforts in 3 aspects: to recruit patients in early phase of illness, to administer rTMS of different protocols according to the symptoms and cognition, and to associate the biotypes of functional connectivity with rTMS's efficacy. All subjects will receive MRI scan before rTMS intervention in the present study. The clinical efficacy of rTMS of the present protocol will be applied to validate the biotypes of functional connectivity in early psychosis. The biotypes will be determined using an existing independent dataset, which include 650 available cases of resting MRI (including 400 patients in prodromal phase, 100 patients with first episode and 150 controls).

Individual rTMS target will be optimized basing individual neuroimaging navigation. In the present protocol, we will recruit 300 new cases and perform a multicenter and randomized clinical trial to test the efficacy of our optimized rTMS protocols. All patients will be stratified according to their negative symptoms, positive symptom and cognition, and this will be determined by a panel of psychiatrists and rTMS therapists. It is estimated that about 100 cases in each of three subgroups. Subgroup 1 is characterized by prominent negative symptoms and will receives rTMS over cerebellum and right dorsolateral prefrontal cortex. Subgroup 2 is characterized by prominent cognition deficits and will receive rTMS over left inferior parietal lobule, navigated by individual MRI and functional connectivity map with left hippocampus. Subgroup 3 is characterized by positive symptoms and will receive deep rTMS over ACC using H7 coil. The present project, if being performed successfully, will promote the non-invasive physical therapy in psychiatry to a significantly higher level.

Conditions

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Schizophrenia; Psychosis First Episode Psychosis Clinical High Risk

Keywords

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schizophrenia prodromal phase biotypes target optimizing precision calculation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Active TMS targeting both cerebellum and right dorsolateral prefrontal cortex.

Subjects identified as with prominent negative symptoms will be randomized into active group, who will receive active rTMS over cerebellum and right dorsolateral prefrontal cortex navigated by individual MRI.

Group Type ACTIVE_COMPARATOR

repetitive transcranial magnetic stimulation (rTMS)

Intervention Type DEVICE

All subjects with early psychosis will be divided into three subgroups determined by their psychotic symptoms and cognition. There are three rTMS strategies: (1) For subgroup 1, characterized by negative symptoms, iTBS over cerebellum and 1 Hz over right DLPFC; (2) For subgroup 2, characterized by cognition deficits, 20 Hz over the left inferior parietal cortex; (3) For subgroup 3, characterized by positive symptoms: 10 Hz over ACC. Ten to twenty sessions of rTMS will be delivered to each patients during the intervention period.

Sham TMS targeting both cerebellum and right dorsolateral prefrontal cortex

Subjects identified as with prominent negative symptoms will be randomized into sham group, who will receive sham rTMS over cerebellum and right dorsolateral prefrontal cortex navigated by individual MRI.

Group Type SHAM_COMPARATOR

repetitive transcranial magnetic stimulation (rTMS)

Intervention Type DEVICE

All subjects with early psychosis will be divided into three subgroups determined by their psychotic symptoms and cognition. There are three rTMS strategies: (1) For subgroup 1, characterized by negative symptoms, iTBS over cerebellum and 1 Hz over right DLPFC; (2) For subgroup 2, characterized by cognition deficits, 20 Hz over the left inferior parietal cortex; (3) For subgroup 3, characterized by positive symptoms: 10 Hz over ACC. Ten to twenty sessions of rTMS will be delivered to each patients during the intervention period.

Active TMS targeting left inferior parietal lobule

Subjects identified with prominent cognition deficits wil be randomized into active group, who will receive active rTMS over left inferior parietal lobule, navigated by individual MRI and functional connectivity map with left hippocampus.

Group Type ACTIVE_COMPARATOR

repetitive transcranial magnetic stimulation (rTMS)

Intervention Type DEVICE

All subjects with early psychosis will be divided into three subgroups determined by their psychotic symptoms and cognition. There are three rTMS strategies: (1) For subgroup 1, characterized by negative symptoms, iTBS over cerebellum and 1 Hz over right DLPFC; (2) For subgroup 2, characterized by cognition deficits, 20 Hz over the left inferior parietal cortex; (3) For subgroup 3, characterized by positive symptoms: 10 Hz over ACC. Ten to twenty sessions of rTMS will be delivered to each patients during the intervention period.

Sham TMS targeting left inferior parietal lobule

Subjects identified with prominent cognition deficits wil be randomized into sham group, who will receive sham rTMS over left inferior parietal lobule, navigated by individual MRI and functional connectivity map with left hippocampus.

Group Type PLACEBO_COMPARATOR

repetitive transcranial magnetic stimulation (rTMS)

Intervention Type DEVICE

All subjects with early psychosis will be divided into three subgroups determined by their psychotic symptoms and cognition. There are three rTMS strategies: (1) For subgroup 1, characterized by negative symptoms, iTBS over cerebellum and 1 Hz over right DLPFC; (2) For subgroup 2, characterized by cognition deficits, 20 Hz over the left inferior parietal cortex; (3) For subgroup 3, characterized by positive symptoms: 10 Hz over ACC. Ten to twenty sessions of rTMS will be delivered to each patients during the intervention period.

Active deep TMS using Brainways H7 coil targeting ACC

Subjects identified as with positive symptoms will be randomized into active group, who will receive active deep rTMS over ACC using H7 coil.

Group Type ACTIVE_COMPARATOR

repetitive transcranial magnetic stimulation (rTMS)

Intervention Type DEVICE

All subjects with early psychosis will be divided into three subgroups determined by their psychotic symptoms and cognition. There are three rTMS strategies: (1) For subgroup 1, characterized by negative symptoms, iTBS over cerebellum and 1 Hz over right DLPFC; (2) For subgroup 2, characterized by cognition deficits, 20 Hz over the left inferior parietal cortex; (3) For subgroup 3, characterized by positive symptoms: 10 Hz over ACC. Ten to twenty sessions of rTMS will be delivered to each patients during the intervention period.

Sham deep TMS using Brainways H7 coil targeting ACC

Subjects identified with positive symptoms will be randomized into sham group, who will receive sham deep rTMS over ACC using H7 coil.

Group Type PLACEBO_COMPARATOR

repetitive transcranial magnetic stimulation (rTMS)

Intervention Type DEVICE

All subjects with early psychosis will be divided into three subgroups determined by their psychotic symptoms and cognition. There are three rTMS strategies: (1) For subgroup 1, characterized by negative symptoms, iTBS over cerebellum and 1 Hz over right DLPFC; (2) For subgroup 2, characterized by cognition deficits, 20 Hz over the left inferior parietal cortex; (3) For subgroup 3, characterized by positive symptoms: 10 Hz over ACC. Ten to twenty sessions of rTMS will be delivered to each patients during the intervention period.

Interventions

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repetitive transcranial magnetic stimulation (rTMS)

All subjects with early psychosis will be divided into three subgroups determined by their psychotic symptoms and cognition. There are three rTMS strategies: (1) For subgroup 1, characterized by negative symptoms, iTBS over cerebellum and 1 Hz over right DLPFC; (2) For subgroup 2, characterized by cognition deficits, 20 Hz over the left inferior parietal cortex; (3) For subgroup 3, characterized by positive symptoms: 10 Hz over ACC. Ten to twenty sessions of rTMS will be delivered to each patients during the intervention period.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Meeting the syndrome of clinical high risk of psychosis, identified by a face-to-face interview using the Chinese version of Structured Interview for Prodromal Syndromes / Scale of Prodromal Symptoms (SIPS/SOPS);
* Given the written consent for participation.
* Age between 14-45 years old;
* IQ\>69;
* PANSS total scores \>= 55 or BVMT-R score \<= 26;


* Meeting the DSM-V diagnostic criteria for schizophrenia spectrum disorders;
* Given the written consent for participation.
* Age between 14-45 years old;
* IQ\>69;
* during the first episode without a full remission;
* PANSS total scores \>= 55 or BVMT-R score \<= 26;
* within receiving rTMS, patients can receive second-generation antipsychotics except clozapine with stable dosages

Exclusion Criteria

* any contraindication to TMS treatment or magnetic resonance imaging (MRI)
* substance or alcohol abuse within recent three months
* any sensorimotor disorder (e.g., hearing disorder, lose one's sight), or any neurological disease (brain injury, epilepsy ) or any other physical disease which may lead to psychotic symptoms.

For subjects with first-episode schizophrenia


* any contraindication to TMS treatment or magnetic resonance imaging (MRI)
* substance or alcohol abuse within recent three months
* any sensorimotor disorder (e.g., hearing disorder, lose one's sight), or any neurological disease (brain injury, epilepsy) or any other physical disease which may lead to psychotic symptoms.
Minimum Eligible Age

14 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Suzhou Psychiatric Hospital

OTHER

Sponsor Role collaborator

Guangzhou Psychiatric Hospital

OTHER_GOV

Sponsor Role collaborator

Shenzhen Kangning Hospital

OTHER

Sponsor Role collaborator

Tianjin Anding Hospital

OTHER

Sponsor Role collaborator

Nantong Fourth People's Hospital & Nantong Brain Hospital

UNKNOWN

Sponsor Role collaborator

Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Jijun Wang

Professor of Department of Psychiatry

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jijun Wang, M.D., Ph.D

Role: PRINCIPAL_INVESTIGATOR

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine

Locations

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The Affiliated Brain Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status NOT_YET_RECRUITING

Nantong Fourth People's Hospital & Nantong Brain Hospital

Nantong, Jiangsu, China

Site Status RECRUITING

Suzhou Guangji Hospital

Suzhou, Jiangsu, China

Site Status RECRUITING

Shanghai Mental Health Center

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Shenzhen Kangning Hospital

Shenzhen, , China

Site Status RECRUITING

Tianjin Anding Hospital

Tianjin, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Jijun Wang, M.D, Ph.D

Role: CONTACT

Phone: 86-21-34773065

Email: [email protected]

Facility Contacts

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Liping Cao

Role: primary

Xing Chen

Role: primary

Li Hui, PhD

Role: primary

Jijun Wang, MD, PhD

Role: primary

Lingyun Zeng

Role: primary

Bin Zhang

Role: primary

References

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Cui H, Giuliano AJ, Zhang T, Xu L, Wei Y, Tang Y, Qian Z, Stone LM, Li H, Whitfield-Gabrieli S, Niznikiewicz M, Keshavan MS, Shenton ME, Wang J, Stone WS. Cognitive dysfunction in a psychotropic medication-naive, clinical high-risk sample from the ShangHai-At-Risk-for-Psychosis (SHARP) study: Associations with clinical outcomes. Schizophr Res. 2020 Dec;226:138-146. doi: 10.1016/j.schres.2020.06.018. Epub 2020 Jul 18.

Reference Type BACKGROUND
PMID: 32694037 (View on PubMed)

Wang J, Zhou Y, Gan H, Pang J, Li H, Wang J, Li C. Efficacy Towards Negative Symptoms and Safety of Repetitive Transcranial Magnetic Stimulation Treatment for Patients with Schizophrenia: A Systematic Review. Shanghai Arch Psychiatry. 2017 Apr 25;29(2):61-76. doi: 10.11919/j.issn.1002-0829.217024.

Reference Type BACKGROUND
PMID: 28765677 (View on PubMed)

Zhuo K, Tang Y, Song Z, Wang Y, Wang J, Qian Z, Li H, Xiang Q, Chen T, Yang Z, Xu Y, Fan X, Wang J, Liu D. Repetitive transcranial magnetic stimulation as an adjunctive treatment for negative symptoms and cognitive impairment in patients with schizophrenia: a randomized, double-blind, sham-controlled trial. Neuropsychiatr Dis Treat. 2019 May 8;15:1141-1150. doi: 10.2147/NDT.S196086. eCollection 2019.

Reference Type BACKGROUND
PMID: 31190822 (View on PubMed)

Brady RO Jr, Gonsalvez I, Lee I, Ongur D, Seidman LJ, Schmahmann JD, Eack SM, Keshavan MS, Pascual-Leone A, Halko MA. Cerebellar-Prefrontal Network Connectivity and Negative Symptoms in Schizophrenia. Am J Psychiatry. 2019 Jul 1;176(7):512-520. doi: 10.1176/appi.ajp.2018.18040429. Epub 2019 Jan 30.

Reference Type BACKGROUND
PMID: 30696271 (View on PubMed)

Tang Y, Jiao X, Wang J, Zhu T, Zhou J, Qian Z, Zhang T, Cui H, Li H, Tang X, Xu L, Zhang L, Wei Y, Sheng J, Liu L, Wang J. Dynamic Functional Connectivity Within the Fronto-Limbic Network Induced by Intermittent Theta-Burst Stimulation: A Pilot Study. Front Neurosci. 2019 Sep 13;13:944. doi: 10.3389/fnins.2019.00944. eCollection 2019.

Reference Type BACKGROUND
PMID: 31572111 (View on PubMed)

Tang Y, Xu L, Zhu T, Cui H, Qian Z, Kong G, Tang X, Wei Y, Zhang T, Hu Y, Sheng J, Wang J. Visuospatial Learning Selectively Enhanced by Personalized Transcranial Magnetic Stimulation over Parieto-Hippocampal Network among Patients at Clinical High-Risk for Psychosis. Schizophr Bull. 2023 Jul 4;49(4):923-932. doi: 10.1093/schbul/sbad015.

Reference Type BACKGROUND
PMID: 36841956 (View on PubMed)

Wang J, Wei Y, Hu Q, Tang Y, Zhu H, Wang J. The efficacy and safety of dual-target rTMS over dorsolateral prefrontal cortex (DLPFC) and cerebellum in the treatment of negative symptoms in first-episode schizophrenia: Protocol for a multicenter, randomized, double-blind, sham-controlled study. Schizophr Res Cogn. 2024 Nov 29;39:100339. doi: 10.1016/j.scog.2024.100339. eCollection 2025 Mar.

Reference Type DERIVED
PMID: 39687049 (View on PubMed)

Other Identifiers

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CRC2018ZD01

Identifier Type: -

Identifier Source: org_study_id