An interventional study of Transcranial Temporal Interference Stimulation (tTIS) in Spinocerebellar Ataxia Type 3, sponsored by First Affiliated Hospital of Fujian Medical University. Not yet recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-09-01.
Sponsored by First Affiliated Hospital of Fujian Medical University · Not applicable, Interventional, and Treatment
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.
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.
33 studies on the registry are indexed under Machado-Joseph Disease; 5 are open to participants now.
This study's planned enrollment of 24 is close to the median of 23 across 21 interventional studies indexed under Machado-Joseph Disease.
Browse Machado-Joseph Disease studies →First Affiliated Hospital of Fujian Medical University is the lead sponsor of 97 studies on the registry; 55 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Transcranial Temporal Interference Stimulation (tTIS) uses a difference frequency (Δf) of 30 Hz.
Device: Transcranial Temporal Interference Stimulation (tTIS)
Transcranial Temporal Interference Stimulation (tTIS) uses a difference frequency (Δf) of 40 Hz.
Device: Transcranial Temporal Interference Stimulation (tTIS)
Transcranial Temporal Interference Stimulation (tTIS) uses a difference frequency (Δf) of 70 Hz.
Device: 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.
Safety: Incidence of Dose-Limiting Toxicity (DLT)
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
Time frame: 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
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.
Time frame: Baseline and within 24 hours after completing the 5-day tTIS treatment
Comprehensive Benefit-Risk: Utility
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.
Time frame: Within 24 hours after completing the 5-day tTIS treatment
The International Cooperative Ataxia Rating Scale (ICARS)
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.
Time frame: Baseline and within 24 hours after completing the 5-day tTIS treatment
The European Quality of Life 5-Dimension (EQ-5D)
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.
Time frame: Baseline and within 24 hours after completing the 5-day tTIS treatment
Patient Global Impression of Change (PGI-C)
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
Time frame: Within 24 hours after completing the 5-day tTIS treatment
Clinical Global Impression of Change (CGI-C)
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
Time frame: Within 24 hours after completing the 5-day tTIS treatment
Change in Multimodal Magnetic Resonance Imaging (MRI) Parameters
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.
Time frame: Baseline and within 24 hours after completing the 5-day tTIS treatment
Functional Near-Infrared Spectroscopy (fNIRS) assesses hemodynamic changes
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.
Time frame: Baseline and within 24 hours after completing the 5-day tTIS treatment
Plan to share: No
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First Affiliated Hospital of Fujian Medical University