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

First Episode Psychosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04853485
• Other study ID #: CRC2018ZD01
• Status: Recruiting
• Phase: N/A
• Start date: August 1, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: December 2023
• Source: Shanghai Jiao Tong University School of Medicine
• Contact: Jijun Wang, M.D, Ph.D
• Phone: 86-21-34773065
• Email: jijunwang27[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 45 Years

Eligibility

For subjects at clinical high-risk for psychosis

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;

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

Inclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Clinical High Risk
• First Episode Psychosis
• Mental Disorders
• Psychotic Disorders
• Schizophrenia
• Schizophrenia; Psychosis

Intervention

Device:
• 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.

Locations

Country	Name	City	State
China	The Affiliated Brain Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Nantong Fourth People's Hospital & Nantong Brain Hospital	Nantong	Jiang Su
China	Shanghai Mental Health Center	Shanghai	Shanghai
China	Shenzhen Kangning Hospital	Shenzhen
China	Suzhou Guangji Hospital	Suzhou	Jiangsu
China	Tianjin Anding Hospital	Tianjin

Sponsors (6)

Lead Sponsor	Collaborator
Shanghai Jiao Tong University School of Medicine	Guangzhou Psychiatric Hospital, Nantong Fourth People's Hospital & Nantong Brain Hospital, Shenzhen Kangning Hospital, Suzhou Psychiatric Hospital, Tianjin Anding Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate (the number of non-responders) for subgroup 1 and subgroup 3	Response or responder will be determined by the reduction of PANSS total scores >= 25%	Within 24 hours after the rTMS intervention
Primary	Improvement on cognition for subgroup 2	Change in BVMT-R score as measured by MCCB	Within 24 hours after the rTMS intervention
Secondary	Improvement of psychotic symptoms	The changes of PANSS scores and sub-scale scores	Within 24 hours after the rTMS intervention
Secondary	Improvement of prodromal symptoms	The changes of SOPS scores and sub-scale scores	Within 24 hours after the rTMS intervention
Secondary	Improvement of cognitive function	The changes of all cognitive domains assessed by MCCB	Within 24 hours after the rTMS intervention
Secondary	Improvement of global functioning	The GAF changes	Within 24 hours after the rTMS intervention
Secondary	Functional connectivity	changes of whole-brain functional connectivity patterns	Within 1week after the rTMS intervention
Secondary	side effect and safety	the frequency and severity of side effects	during and after rTMS intervention
Secondary	clinical outcome	remission, non-remission or relapse	1 year
Secondary	The accuracy of prediction with functional connectivity biotypes at baseline	The association of clinical outcomes after rTMS intervention with functional connectivity biotypes at baseline	1 year
Secondary	change in individualized psychosis risk score	For subjects at clinical high risk of psychosis, individualized psychosis risk score will be calculated using clinical symptoms and cognition, which indicate the psychosis risk in the future.	Within 24 hours after the rTMS intervention