Optimizing Parameters of Transcranial Temporal Interference Stimulation for Spinocerebellar Ataxia Type 3

Официальное название

Efficacy and Safety of Transcranial Temporal Interference Stimulation of the Cerebellar Dentate Nucleus Using Individualized Head Modeling in Patients With Spinocerebellar Ataxia Type 3

Обзор

The purpose of this research study is to identify the optimal biological dose for tTIS that targets DN in SCA3 while achieving the best possible balance between therapeutic efficacy and safety.

Подробное описание

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansion in the ATXN3 gene. Selective degeneration of neurons in the cerebellar dentate nucleus (DN) leads to abnormal cerebellar outflow circuitry and impaired motor control, resulting in progressive gait ataxia, dysarthria and other motor symptoms. Current treatments are symptomatic only, with no disease-modifying therapies available. Deep brain stimulation targeting the dentate nucleus has shown efficacy but is invasive and associated with significant adverse events.

Transcranial temporal interference stimulation (tTIS) enables non-invasive, deep and spatially precise neuromodulation. It has been applied in various neurological and psychiatric disorders with favorable safety and efficacy, demonstrating potential for neuromodulation of deep cerebellar circuits.

This phase I/II adaptive dose-finding prospective interventional study evaluates the safety and efficacy of tTIS targeting the cerebellar dentate nucleus in patients with spinocerebellar ataxia type 3. Using MRI-derived individualized head models and real-time neuronavigation, the study employs a utility-based Bayesian optimal interval (U-BOIN) design with three difference frequencies: 30 Hz, 40 Hz, and 70 Hz. Patients are enrolled in sequential cohorts of three, with dose escalation guided by a utility-based approach integrating safety and efficacy data. Each patient receives ten tTIS sessions over two consecutive weeks, with one session daily. Motor function, balance function, activities of daily living, and multimodal magnetic resonance imaging are evaluated before the first treatment session and after the final treatment session.

Вмешательства

• Устройство Transcranial Temporal Interference Stimulation (tTIS)
  Participants assigned to this intervention arm receive transcranial temporal interference stimulation (tTIS) with a difference frequency (Δf) of 30Hz/40Hz/70 Hz. Before treatment, individualized electric field modeling is performed based on each participant's 3D-T1 MRI data to optimize electrode placement and stimulation parameters. The stimulation target is the bilateral cerebellar dentate nuclei. A personalized finite element head model is generated, and electrode positions are determined thr

Первичные конечные точки

• Safety: Incidence of Dose-Limiting Toxicity (DLT) [Срок оценки: At any point during or immediately following intervention on day of tTIS application]
• Efficacy: To assess the proportion of patients with SARA improvement (decrease) of at least 1.5 from baseline after 5 days [Срок оценки: Baseline and within 24 hours after completing the 5-day tTIS treatment]
• Comprehensive Benefit-Risk: Utility [Срок оценки: Within 24 hours after completing the 5-day tTIS treatment]

Критерии участия

Критерии включения

• A physician-diagnosed SCA3 according to diagnostic criteria, with definite clinical symptoms and confirmed genetic testing;
• Age 18-75 years;
• Baseline total score of SARA: 8-30 points (inclusive); SARA gait function subscore: 2-6 points (inclusive);
• Willing to participate and provide informed consent;
• Have a reliable caregiver available;
• No severe cognitive impairment that would preclude reliable reporting of adverse events or efficacy during treatment.

Критерии исключения

• History of seizures or convulsions, or a seizure within 6 months prior to enrolment;
• History of severe traumatic brain injury or intracranial neurosurgery;
• Presence of cardiac pacemakers, cochlear implants, intracranial implanted electronic devices, or other MRI-contraindicated ferromagnetic implants;
• Severe cognitive impairment (Mini-Mental State Examination \[MMSE\] score ≤ 9) or severe visual, auditory, or speech dysfunction preventing cooperation with scale assessments and study procedures;
• Pregnant or lactating women, or women of childbearing age not using reliable contraception;
• Previous neuromodulation treatment (e.g., rTMS or tDCS) within the past year;
• Skin breakdown or inflammation at the electrode placement site, or known allergy to conductive gel or electrode patch adhesives;
• Currently participating in other interventional clinical trials, or planning to participate in other trials that might affect the outcome assessment of this study during the study period.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Department of Rehabilitation Medicine, The First Affiliated Hospital of Fujian Medical Uni — Фучжоу

Идентификаторы

NCT: NCT07743866 · MRCTA,ECFAH of FMU[2026]803

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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