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TIS for Improving Cognitive Impairment in Schizophrenia

9 de junho de 2026 atualizado por: Renrong Wu, Central South University

Efficacy and Safety of Time Interference Stimulation on Cognitive Impairment in Patients With Schizophrenia

This study aims to evaluate the efficacy, safety, and underlying neural mechanisms of TIS targeting the hippocampus in ameliorating cognitive impairment associated with schizophrenia (CIAS). Researchers will compare active TIS to a sham control to see if TIS works to treat CIAS. Participants will receive TIS twice a day for 2 weeks. Their clinical data, including the baseline clinical symptom scale score, cognitive function, E/I imbalance index recorded by EEG, and MRI data, will be collected at baseline, at the end of the 2-week intervention, and 4 weeks after the intervention.

Visão geral do estudo

Status

Ainda não está recrutando

Condições

Intervenção / Tratamento

Descrição detalhada

Schizophrenia is a chronic psychiatric disorder that imposes a substantial and increasing global disease burden. Cognitive impairment associated with schizophrenia (CIAS) is a core deficit that strongly predicts global function and quality of life. While effective for positive symptoms, antipsychotics cannot meet treatment requirements on CIAS and are limited by severe metabolic and extrapyramidal side effects. Consequently, there is an urgent need to explore effective treatments for CIAS.

Non-invasive brain stimulation (NIBS), including TMS and TES, has emerged as a promising adjunctive therapy for CIAS by modulating cortical excitability and neuroplasticity. However, conventional NIBS is constrained by limited focal depth, indirectly influencing subcortical circuits. Temporal Interference Stimulation (TIS) overcomes these limitations by utilizing intersecting high-frequency electric fields to generate a low-frequency envelope, enabling the selective modulation of deep neural targets while sparing the superficial cortex. TIS offers superior spatial precision and tolerability for treating neuropsychiatric disorders involving deep-circuit dysfunction.

Neurophysiological evidence implicates glutamatergic dysregulation and excitatory-inhibitory (E/I) imbalance as key mechanisms in schizophrenia. Hippocampal hyperactivity enhances excitatory drive to the prefrontal cortex, disrupting cortico-hippocampal communication, attenuating γ-band oscillations, and impairing network synchrony that supports working memory and executive processes.

Recent studies in healthy individuals demonstrate that 5 Hz TIS targeting the left anterior hippocampus enhances episodic memory and hippocampal-prefrontal connectivity. Intermittent theta-burst stimulation (iTBS) of the right hippocampus improves spatial memory. Only one pilot study in schizophrenia has examined high-frequency (130 Hz) TIS targeting the right nucleus accumbens, showing improvements in negative and cognitive symptoms.

This study aims to evaluate the efficacy and underlying neural mechanisms of TIS targeting the hippocampus in ameliorating CIAS.

We will conduct a randomized controlled clinical trial. 50 participants with schizophrenia (25 in each group) will be recruited and randomly assigned to an active treatment group or a sham treatment group. The intervention will be given twice a day for 2 weeks. The changes in clinical symptoms, cognitive function, E/I imbalance, and brain structure and function will be collected at baseline, at the end of the 2-week intervention, and 4 weeks after the intervention to explore the short-term efficacy, safety, and neurobiological mechanism of TIS in improving cognitive function in schizophrenia.

Tipo de estudo

Intervencional

Inscrição (Estimado)

50

Estágio

  • Não aplicável

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Locais de estudo

  • China
    • Hunan
      • Changsha, Hunan, China, 410011
        • Second Xiangya Hospital, Central South University
        • Contato:

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto

Aceita Voluntários Saudáveis

Não

Descrição

Inclusion Criteria:

  • Age 18-50 years old;
  • meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth edition (DSM-5) diagnostic criteria;
  • the diagnosis of schizophrenia is confirmed by the Structured Clinical Interview for DSM-5 (SCID-5);
  • the disease duration does not exceed 8 years;
  • 1-2 antipsychotic drugs are taken, and the treatment dose of antipsychotic drugs was stable for at least 1 week before enrollment. Mood stabilizers, antidepressants, and excessive benzodiazepines (lorazepam when 2 doses exceeded 2 mg/d) are not allowed;
  • The type of antipsychotic drugs remains unchanged during treatment, and the dose is adjusted by no more than 25%;
  • Impaired functioning in daily activities;
  • The Global Deficit Score (GDS) for the MATRICS Consensus Cognitive Battery (MCCB) reaches 0.5 or above;
  • Agree to participate in this study and provide written informed consent

Exclusion Criteria:

  • Presence of other psychiatric comorbidities, intellectual disability, obvious mood symptoms, or substance use disorders (other than caffeine and/or tobacco);
  • with clear drug-induced extrapyramidal reaction;
  • A history of seizures, meningitis, or encephalitis;
  • with contraindications to transcranial electrical stimulation;
  • History of intracranial tumors or surgery;
  • history of severe head trauma;
  • have received other regimens of electrical or magnetic therapy in 1 month before enrollment.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Triplo

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Active TIS
Active TIS group will be administered active temporal interference stimulation
Dispositivo: temporal interference stimulation
TIS will use 2 pairs of electrodes placed according to a 10-10 EEG system and fixed with conductive paste to produce a theta burst stimulation pattern. Electric field modeling will be performed utilizing MRI T1 images to optimize the individualized electrode configuration to generate electric field intensities above 0.6 V/m in the hippocampus of each patient. Each session of stimulation lasts 30 minutes.
Comparador Falso: sham TIS
Sham TIS group will be administered sham temporal interference stimulation
Dispositivo: Sham stimulation
The sham stimulation only includes a 15-second ramp-up at the start and ramp-down at the beginning of each stimulus, which could simulate the scalp pulsing sensation caused by the change of current at the beginning and end of the stimulus.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
changes on MCCB scores
Prazo: Baseline, after 2-week intervention, 4 weeks post-treatment
The MATRICS Consensus Cognitive Battery (MCCB) can be used for cognitive assessment of schizophrenia, bipolar disorder, and other neuropsychiatric diseases. The MCCB covers nine cognitive domains, including attention, information processing speed, verbal learning and memory, visual learning and memory, spatial working memory, reasoning, problem solving, social cognition, executive function, and fine motor skills. The working memory domain does not include verbal working memory because the Chinese language would not make feasible the inclusion of the LNS test.
Baseline, after 2-week intervention, 4 weeks post-treatment

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Alterações na função cerebral
Prazo: Linha de base, após intervenção de 2 semanas
A ressonância magnética funcional (fMRI) baseia-se no contraste dependente do nível de oxigénio no sangue (BOLD) que pode detetar alterações na oxigenação sanguínea para analisar a mudança da função cerebral após a intervenção.
Linha de base, após intervenção de 2 semanas
Changes in Positive and Negative Symptom Scale (PANSS) scores
Prazo: Baseline, after 2-week intervention, 4 weeks post-treatment
Range from 30 to 210, higher score indicates more severe positive and negative symptoms.
Baseline, after 2-week intervention, 4 weeks post-treatment
Change in Scale for Assessment of Negative Symptoms (SANS) score
Prazo: Baseline, after 2-week intervention, 4 weeks post-treatment
The score range is 0-120; the higher the score, the more severe the negative symptoms are.
Baseline, after 2-week intervention, 4 weeks post-treatment
Changes in Calgary Depression Scale for Schizophrenia (CDSS) score
Prazo: Baseline, after 2-week intervention, 4 weeks post-treatment
Ranges from 0 to 27; a higher score indicates more severe affective symptoms.
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on neuroelectrophysiological signals
Prazo: Baseline, after 2-week intervention, 4 weeks post-treatment
The changes of neuroelectrophysiological signals were collected under the task-based electroencephalogram.
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on global function
Prazo: Baseline, after 2-week intervention, 4 weeks post-treatment
Global function will be measured by the Global Assessment of Functioning (GAF). GAF is a 0-100 numerical scale used by clinicians to subjectively rate a person's overall psychological, social, and occupational functioning. Higher scores (91-100) indicate superior functioning, while lower scores (1-10) indicate severe danger or impairment.
Baseline, after 2-week intervention, 4 weeks post-treatment
changes in social function.
Prazo: Baseline, 4 weeks post-treatment
Social function will be assessed by the Global Functioning: Social (GF:Social) and Role (GF:Role) scales (GFS) and the Social Functioning Scale (SFS). The GFS is a clinician-rated, 1-10 point tool designed to measure social and occupational functioning. They focus on development, allowing for the assessment of change over time, and avoid confounding functioning with psychiatric symptoms. The SFS is a 79-item self-report measure designed to assess social functioning in schizophrenia. Items assess ability and performance related to social engagement, interpersonal contact, recreation, independence and competence in activities, activities of daily living, and employment.
Baseline, 4 weeks post-treatment
changes on aperiodic 1/f-like signal exponent
Prazo: Baseline, after 2-week intervention, 4 weeks post-treatment
The aperiodic component of the neural power spectrum, quantified as the slope of the 1/f-like signal recorded by electroencephalogram, will be used as an index of excitation/inhibition balance. The unit of measure is the exponent (unitless).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on long-range temporal correlations (LRTCs)
Prazo: Baseline, after 2-week intervention, 4 weeks post-treatment
Long-range temporal correlations of neural oscillations recorded by electroencephalogram will be measured as an index of the temporal stability of excitation/inhibition balance. The unit of measure is the Hurst exponent (unitless).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on functional E/I ratio
Prazo: Baseline, after 2-week intervention, 4 weeks post-treatment
The ratio of excitatory to inhibitory neural activity derived from electroencephalogram signals will be calculated as a functional excitation/inhibition balance index. The unit of measure is a ratio (unitless).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on oscillation power across all frequency bands
Prazo: Baseline, after 2-week intervention, 4 weeks post-treatment
The power of neural oscillations across all frequency bands (e.g., delta, theta, alpha, beta, gamma) recorded by electroencephalogram will be measured. The power values from all bands will be averaged to produce a single composite oscillation power index. The unit of measure is microvolts squared (μV²).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on 40 Hz auditory steady-state responses (40Hz-ASSRs)
Prazo: Baseline, after 2-week intervention, 4 weeks post-treatment
The 40 Hz auditory steady-state responses recorded by electroencephalogram will be measured, including both evoked power and inter-trial phase coherence. The unit of measure for evoked power is μV², and the unit of measure for phase coherence is unitless.
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on mismatch negativity (MMN)
Prazo: Baseline, after 2-week intervention, 4 weeks post-treatment
The mismatch negativity amplitude recorded by electroencephalogram using an oddball paradigm will be measured. The unit of measure is microvolts (μV).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on P300 event-related potential
Prazo: Baseline, after 2-week intervention, 4 weeks post-treatment
The P300 amplitude recorded by electroencephalogram using an oddball paradigm will be measured. The unit of measure is microvolts (μV).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on behavioral performance - Sternberg Item-Recognition Paradigm
Prazo: Baseline, after 2-week intervention, 4 weeks post-treatment
Behavioral performance will be evaluated using the Sternberg Item-Recognition Paradigm, a memory task that measures reaction time and accuracy. The unit of measure for reaction time is milliseconds (ms), and the unit of measure for accuracy is percentage correct (%).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on behavioral performance - Mnemonic Similarity Task
Prazo: Baseline, after 2-week intervention, 4 weeks post-treatment
Behavioral performance will be evaluated using the Mnemonic Similarity Task, a memory task that measures pattern separation and recognition memory. Three indices will be derived and reported separately: the Lure Discrimination Index (LDI), the similarity object recognition index, and the old object recognition index. All three indices are measured in d-prime (unitless).
Baseline, after 2-week intervention, 4 weeks post-treatment
changes on peripheral blood allostatic load index
Prazo: Baseline, 4 weeks post-treatment
Approximately 10 mL of blood will be collected intravenously to measure peripheral blood biomarkers: brain-derived neurotrophic factor (BDNF) in ng/mL, C-reactive protein (CRP) in mg/L, interleukin-6 (IL-6) in pg/mL, Kynurenic acid in nM, high-density lipoprotein (HDL) in mg/dL, low-density lipoprotein (LDL) in mg/dL, and triglycerides (TG) in mg/dL. These biomarkers will be combined into a single allostatic load index using a standardized high-risk count algorithm. For each biomarker, a cutoff score based on population norms or clinical thresholds (e.g., highest-risk quartile) will be applied to determine high-risk status (1 = high-risk, 0 = not high-risk). The allostatic load score is the sum of high-risk indicators across all biomarkers. The unit of measure is the allostatic load score (unitless, integer count).
Baseline, 4 weeks post-treatment

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Central South University

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Estimado)

30 de maio de 2026

Conclusão Primária (Estimado)

1 de dezembro de 2026

Conclusão do estudo (Estimado)

30 de dezembro de 2026

Datas de inscrição no estudo

Enviado pela primeira vez

27 de fevereiro de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

9 de junho de 2026

Primeira postagem (Real)

15 de junho de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

15 de junho de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

9 de junho de 2026

Última verificação

1 de junho de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • TIS20250606
  • 82325020 (Número de outro subsídio/financiamento: National Natural Science Foundation of China)

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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