Efficacy of Cerebellar Transcranial Magnetic Stimulation to Treat Hereditary Spinocerebellar Ataxias

Clinical Study on the Effecacy of Transcranial Magnetic Stimulation of Intermittent Theta Pulse Stimulation(iTBS) Navigated Targeting the Cerebellum in the Treatment of Hereditary Spinocerebellar Ataxia

Spinocerebellar ataxia (SCA) is a type of autosomal dominant ataxia and there is currently no effective treatment. The goal of this clinical trial is to learn the efficacy of navigated iTBS (Intermittent theta-burst stimulation) targeting the cerebellum to treat hereditary spinocerebellar ataxias in adults and explore the role and neural plasticity mechanisms. It will also learn about the safety of cerebellar transcranial magnetic stimulation. The main questions it aims to answer are:

1. Does navigated iTBS targeting the cerebellum improve the symptoms and clinical scale score of ataxias?
2. Safety evaluation measures included treatment-related dizziness, head and neck pain, tinnitus, hearing loss, and epilepsy. Adverse reactions were reported by both subjects and investigators.

Participants will:

1. Navigated iTBS targeting the cerebellum or sham stimulation every day for 7 day,
2. Assessments were made at baseline, within 24 hours after the end of treatment, after 12 weeks, and after 24 weeks of telephone follow-up.

Study Overview

• Status: Not yet recruiting
• Conditions: Spinocerebellar Ataxias
• Intervention / Treatment: Device: navigated iTBS (Intermittent theta-burst stimulation) targeting the cerebellum

Detailed Description

1. Gait analysis, electroencephalogram (EEG), functional magnetic resonance (fMRI) and a series of clinic scales were used to further observe the therapeutic effect and reveal the possible mechanism of neuroplasticity.
2. Forty-two iTBS sessions（1,800 pulses per session, 50-minute intersession interval） were delivered as 6 daily sessions over 7 consecutive days at 80% resting motor threshold (adjusted for cortical depth).

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• SCA1/2/3 patients confirmed by genetic testing
• aged 18-65 years
• presence of ataxia with a score3-20 on the Scale for the Assessment and Rating of Ataxia (SARA) and a score<60 on the International Cooperative Ataxia Rating Scale (ICARS)
• Signed informed consent by patients or their family members

Exclusion Criteria:

• Patients with serious medical conditions (such as kidney failure, liver disease) and uncontrolled high blood pressure or diabetes
• Patients with severe cognitive and behavioral disorders or mental illness
• Pregnant and lactating patients; Use other ongoing clinical medications, except for neuroprotective agents such as coenzyme Q10, butylphthalein, or cyticholine; If patients are taking valproate, riluzole and other drugs but they and their guardians have a strong desire for treatment, they can be evaluated again after washout.
• History of stroke, encephalitis and epilepsy
• Pacemakers, electronic devices and intracranial metal objects.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: active stimulation; navigated iTBS (Intermittent theta-burst stimulation) targeting the cerebellum	Device: navigated iTBS (Intermittent theta-burst stimulation) targeting the cerebellum; 1,800 pulses per session for unilateral cerebellum, 50-minute intersession interval, 80% resting motor threshold, total 75600 pulse number.
Sham Comparator: sham stimulation; Sham stimulation was delivered via the built-in mode of the stimulator with 10% RMT intensity.	Device: navigated iTBS (Intermittent theta-burst stimulation) targeting the cerebellum; 1,800 pulses per session for unilateral cerebellum, 50-minute intersession interval, 80% resting motor threshold, total 75600 pulse number.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change from baseline score on ICARS(International Cooperative Ataxia Rating Scale)	International Cooperative Ataxia Rating Scale contains four subscales on a scale of 0 to 100, with higher scores indicating more severe ataxia	at baseline, within 24 hours after the end of treatment, after 12 weeks, and within 24 hours after the end of the second round of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change from baseline score on SARA(Scale for the Assessment and Rating of Ataxia)	Scale for the Assessment and Rating of Ataxia contains eight items on a scale of 0 to 40, with higher scores indicating more severe ataxia	at baseline, within 24 hours after the end of treatment, after 12 weeks, and within 24 hours after the end of the second round of treatment
Gait analysis	The instrumented gait analysis showed that step width, step length	at baseline, within 24 hours after the end of treatment, after 12 weeks, and within 24 hours after the end of the second round of treatment
scalp electroencephalogram	TMS combined with EEG	at baseline, within 24 hours after the end of treatment, after 12 weeks, and within 24 hours after the end of the second round of treatment
Safety evaluation measures	Incidence and severity of side effects	within 24 hours after the end of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change from baseline score on MMSE(Mini-mental state examination)	Assesse cognitive function (orientation, memory, attention, calculation, language ability, etc.)	at baseline, within 24 hours after the end of treatment, after 12 weeks, and within 24 hours after the end of the second round of treatment
MOCA(Montreal Cognitive Scale)	A rapid cognitive assessment tool designed to evaluate cognitive dysfunction, covering 11 assessment items across 8 cognitive domains: attention and concentration, executive function, memory, language, visuospatial skills, abstract thinking, calculation, and orientation.	at baseline, within 24 hours after the end of treatment, after 12 weeks, and within 24 hours after the end of the second round of treatment
HAMA(Hamilton anxiety scale)	Assess the severity of anxiety symptoms in patients	at baseline, within 24 hours after the end of treatment, after 12 weeks, and within 24 hours after the end of the second round of treatment
HAMD(Hamilton depression scale)	Assess the severity of depressive symptoms	at baseline, within 24 hours after the end of treatment, after 12 weeks, and within 24 hours after the end of the second round of treatment
PSQI(Pittsburgh sleep quality Index)	A self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval	at baseline, within 24 hours after the end of treatment, after 12 weeks, and within 24 hours after the end of the second round of treatment
The 9-Hole Peg Test	A common fine motor test used in occupational therapy assessments to collect a baseline on fine motor skills, dexterity, hand-eye coordination, motor planning, and more	at baseline, within 24 hours after the end of treatment, after 12 weeks, and within 24 hours after the end of the second round of treatment
10-m walking test	The 10 Metre Walk Test is a performance measure used to assess walking or gait speed in meters per second over a short distance and can be employed to determine functional mobility, gait, and vestibular function	at baseline, within 24 hours after the end of treatment, after 12 weeks, and within 24 hours after the end of the second round of treatment

Collaborators and Investigators

• Sponsor: Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 20, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: February 4, 2025
• First Submitted That Met QC Criteria: March 20, 2025
• First Posted (Actual): March 27, 2025

Study Record Updates

• Last Update Posted (Actual): March 27, 2025
• Last Update Submitted That Met QC Criteria: March 20, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Dyskinesias; Cerebellar Diseases; Ataxia; Cerebellar Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations
• Other Study ID Numbers: KY20242432

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No