Clinical trial NCT04853485: Repetitive Transcranial Magnetic Stimulation in Early Psychosis and The Functional Connectivity Biotypes
Official title: Repetitive Transcranial Magnetic Stimulation in Subjects With Early Psychosis and The Functional Connectivity Biotypes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Schizophrenia; Psychosis
First Episode Psychosis
Clinical High Risk
Keywords: schizophrenia
prodromal phase
biotypes
target optimizing
precision calculation
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
Collaborators: name: Suzhou Psychiatric Hospital
name: Guangzhou Psychiatric Hospital
name: Shenzhen Kangning Hospital
name: Tianjin Anding Hospital
name: Nantong Fourth People's Hospital & Nantong Brain Hospital
First posted: 2021-04-21
Enrollment: 300
Sex: ALL
Minimum age (years): 14
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Response rate (the number of non-responders) for subgroup 1 and subgroup 3
timeFrame: Within 24 hours after the rTMS intervention
measure: Improvement on cognition for subgroup 2
timeFrame: Within 24 hours after the rTMS intervention
Secondary outcomes:
measure: Improvement of psychotic symptoms
timeFrame: Within 24 hours after the rTMS intervention
measure: Improvement of prodromal symptoms
timeFrame: Within 24 hours after the rTMS intervention
measure: Improvement of cognitive function
timeFrame: Within 24 hours after the rTMS intervention
measure: Improvement of global functioning
timeFrame: Within 24 hours after the rTMS intervention
measure: Functional connectivity
timeFrame: Within 1week after the rTMS intervention
measure: side effect and safety
timeFrame: during and after rTMS intervention
measure: clinical outcome
timeFrame: 1 year
measure: The accuracy of prediction with functional connectivity biotypes at baseline
timeFrame: 1 year
measure: change in individualized psychosis risk score
timeFrame: Within 24 hours after the rTMS intervention
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Affiliated Brain Hospital of Guangzhou Medical University
state: Guangdong
city: Nantong
country: China
facility: Nantong Fourth People's Hospital & Nantong Brain Hospital
state: Jiang Su
city: Suzhou
country: China
facility: Suzhou Guangji Hospital
state: Jiangsu
city: Shanghai
country: China
facility: Shanghai Mental Health Center
state: Shanghai
city: Shenzhen
country: China
facility: Shenzhen Kangning Hospital
city: Tianjin
country: China
facility: Tianjin Anding Hospital
Study officials:
affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine
name: Jijun Wang, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
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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.
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.