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

2026年8月31日 更新者：Xinyuan Chen、First Affiliated Hospital of Fujian Medical University

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

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.

調査の概要

状態

まだ募集していません

条件

介入・治療

詳細な説明

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.

研究の種類

介入

入学 (推定)

24

段階

  • 適用できない

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

  • 名前：Kai-Xiong Chen
  • 電話番号：+86 15280096886
  • メール：1002297884@qq.com

研究場所

  • 中国
    • Fujian
      • Fuzhou、Fujian、中国
        • Department of Rehabilitation Medicine, The First Affiliated Hospital of Fujian Medical University
        • コンタクト：

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

いいえ

説明

Inclusion Criteria:

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

Exclusion Criteria:

  1. History of seizures or convulsions, or a seizure within 6 months prior to enrolment;
  2. History of severe traumatic brain injury or intracranial neurosurgery;
  3. Presence of cardiac pacemakers, cochlear implants, intracranial implanted electronic devices, or other MRI-contraindicated ferromagnetic implants;
  4. 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;
  5. Pregnant or lactating women, or women of childbearing age not using reliable contraception;
  6. Previous neuromodulation treatment (e.g., rTMS or tDCS) within the past year;
  7. Skin breakdown or inflammation at the electrode placement site, or known allergy to conductive gel or electrode patch adhesives;
  8. 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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：非ランダム化
  • 介入モデル：順次割り当て
  • マスキング：独身

武器と介入

参加者グループ / アーム
介入・治療
実験的：30 Hz Difference Frequency tTIS
Transcranial Temporal Interference Stimulation (tTIS) uses a difference frequency (Δf) of 30 Hz.
デバイス：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 through simulation-based optimization to achieve focused interference electric fields at the target region.

During each treatment session, tTIS is delivered using two carrier frequencies of 2000 Hz and 2030Hz/2040Hz/2070 Hz, with a current intensity of 2.0 mA (zero-to-peak). Each session lasts 20 minutes. Treatment is administered twice daily, 5 days per week, for a total of 10 sessions.
実験的：40 Hz Difference Frequency tTIS
Transcranial Temporal Interference Stimulation (tTIS) uses a difference frequency (Δf) of 40 Hz.
デバイス：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 through simulation-based optimization to achieve focused interference electric fields at the target region.

During each treatment session, tTIS is delivered using two carrier frequencies of 2000 Hz and 2030Hz/2040Hz/2070 Hz, with a current intensity of 2.0 mA (zero-to-peak). Each session lasts 20 minutes. Treatment is administered twice daily, 5 days per week, for a total of 10 sessions.
実験的：70 Hz Difference Frequency tTIS
Transcranial Temporal Interference Stimulation (tTIS) uses a difference frequency (Δf) of 70 Hz.
デバイス：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 through simulation-based optimization to achieve focused interference electric fields at the target region.

During each treatment session, tTIS is delivered using two carrier frequencies of 2000 Hz and 2030Hz/2040Hz/2070 Hz, with a current intensity of 2.0 mA (zero-to-peak). Each session lasts 20 minutes. Treatment is administered twice daily, 5 days per week, for a total of 10 sessions.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Safety: Incidence of Dose-Limiting Toxicity (DLT)
時間枠：At any point during or immediately following intervention on day of tTIS application

DLT event is defined as any one of the following 5 categories:

  1. Grade Ⅱ (moderate) or higher adverse events per the NCI-CTCAE grading criteria[1] that require topical or non-invasive intervention, such as skin burns (skin breakdown, blister formation);
  2. Clinically observable seizures during stimulation;
  3. Severe headache with vomiting, confusion, or severe dizziness leading to syncope;
  4. Severe sleep disturbance with psychiatric abnormalities (anxiety, depression, hallucinations, etc.);
  5. New brain lesions on imaging, or decreased apparent diffusion coefficient (ADC) values in the subcortex beneath the stimulation site.

References [1] Antal A, et al. Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines (2017-2025: An update) - endorsed by the European Society for Brain Stimulation (ESBS) and by the International Federation for Clinical Neurophysiology (IFCN). Clin Neurophysiol. 2026. 184: 2111436
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
時間枠：Baseline and within 24 hours after completing the 5-day tTIS treatment

The Scale for the Assessment and Rating of Ataxia (SARA) evaluates the severity of ataxia symptoms, including gait, posture, speech, and limb kinetic functions.

Score range: 0-40 Higher scores indicate more severe ataxia. Response is defined as a reduction of ≥1.5 points from baseline.
Baseline and within 24 hours after completing the 5-day tTIS treatment
Comprehensive Benefit-Risk: Utility
時間枠：Within 24 hours after completing the 5-day tTIS treatment

Utility is a composite measure integrating dose-limiting toxicity (DLT) and efficacy response to quantify the overall benefit-risk balance for each dose group.

During the trial, the Utility value for each dose group is dynamically calculated using the U-BOIN design platform. In Stage II, the Utility value determines dose allocation for subsequent cohorts. At study completion, the dose group with the highest Utility value is identified as the optimal biological dose.
Within 24 hours after completing the 5-day tTIS treatment

その他の成果指標

結果測定
メジャーの説明
時間枠
The International Cooperative Ataxia Rating Scale (ICARS)
時間枠：Baseline and within 24 hours after completing the 5-day tTIS treatment

The International Cooperative Ataxia Rating Scale (ICARS) assesses the severity of cerebellar ataxia across four subscales: posture and gait disturbances, limb kinetic functions, speech disorders, and oculomotor disorders.

Total score range: 0-100 Higher scores indicate more severe ataxia impairment.
Baseline and within 24 hours after completing the 5-day tTIS treatment
The European Quality of Life 5-Dimension (EQ-5D)
時間枠：Baseline and within 24 hours after completing the 5-day tTIS treatment

The European Quality of Life 5-Dimension Utility Index Score (EQ-5D Utility Index) assesses health-related quality of life across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

Participants' health states are described using a five-digit code, with values ranging from 11111 (no problems in any dimension) to 33333 (extreme problems in all dimensions). The health state code is converted into a utility index score using population-specific preference weights. The score is anchored at 1.0 for full health, with lower values indicating poorer health status; values below 0 may occur for health states considered worse than death depending on the applicable value set.
Baseline and within 24 hours after completing the 5-day tTIS treatment
Patient Global Impression of Change (PGI-C)
時間枠：Within 24 hours after completing the 5-day tTIS treatment

The Patient Global Impression of Change (PGI-C) is a patient-reported scale assessing perceived change in overall condition after treatment.

Score range: 1-7 Lower scores indicate greater improvement
Within 24 hours after completing the 5-day tTIS treatment
Clinical Global Impression of Change (CGI-C)
時間枠：Within 24 hours after completing the 5-day tTIS treatment

The Clinical Global Impression of Change (CGI-C) is a clinician-rated scale assessing overall change in the patient's clinical status.

Score range: 1-7 Lower scores indicate greater improvement
Within 24 hours after completing the 5-day tTIS treatment
Change in Multimodal Magnetic Resonance Imaging (MRI) Parameters
時間枠：Baseline and within 24 hours after completing the 5-day tTIS treatment
Multimodal magnetic resonance imaging (MRI), including structural MRI (sMRI), resting-state fMRI (rs-fMRI) and diffusion tensor imaging (DTI), is performed to evaluate cerebral structural and functional alterations.
Baseline and within 24 hours after completing the 5-day tTIS treatment
Functional Near-Infrared Spectroscopy (fNIRS) assesses hemodynamic changes
時間枠：Baseline and within 24 hours after completing the 5-day tTIS treatment

Functional Near-Infrared Spectroscopy (fNIRS) assesses hemodynamic changes by measuring regional cerebral oxygenation in the cerebellar and motor cortical regions.

Changes in oxygenation signals reflect alterations in regional neural activity through neurovascular coupling.
Baseline and within 24 hours after completing the 5-day tTIS treatment

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

First Affiliated Hospital of Fujian Medical University

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2026年8月7日

一次修了 (推定)

2026年11月30日

研究の完了 (推定)

2027年2月28日

試験登録日

最初に提出

2026年7月29日

QC基準を満たした最初の提出物

2026年7月31日

最初の投稿 (実際)

2026年8月4日

学習記録の更新

投稿された最後の更新 (実際)

2026年9月1日

QC基準を満たした最後の更新が送信されました

2026年8月31日

最終確認日

2026年8月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • MRCTA,ECFAH of FMU[2026]803

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個々の参加者データ (IPD) を共有する予定はありますか?

いいえ

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