Treatment of Transcranial Alternating Current Stimulation（tACS）on Cerebellar Ataxia

The Treatment of Transcranial Alternating Current Stimulation（tACS）on Patients With Cerebellar Ataxia: A Randomized, Triple-blind, Parallel-controlled Study

This is a longitudinal, triple-blind, randomized-controlled, prospective observational study assessing patients with cerebellar ataxia, including spinocerebellar ataxia type 3 (SCA3) and multiple system atrophy-cerebellar type (MSA-C), to examine the efficacy, safety, and tolerability of transcranial alternating current stimulation (tACS) for up to 3 months.

Study Overview

• Status: Recruiting
• Conditions: Spinocerebellar Ataxia Type 3; Multiple System Atrophy-cerebellar Type
• Intervention / Treatment: Device: Transcranial Alternating Current Stimulation

Detailed Description

Transcranial alternating current stimulation (tACS) is a relatively recent method that noninvasively modulates brain oscillations, and can effectively stimulate deep brain regions, affect brain rhythm, increase neural plasticity, change neurotransmitter levels, and improve brain function. It is a comfortable, safe, effective, non-invasive, and easy-to-operate method, which means it has development potential in relevant medical fields. It has been approved by the FDA for clinically treating neuropsychiatric diseases.

This is a prospective, longitudinal, triple-blind, randomized-controlled, observational study designed to evaluate the efficacy, safety, and tolerability of tACS in patients of SCA3 and MSA-C in China. Based on typical guidelines, we will use the tACS paradigm (bilateral mandible as a place for active electrode stimulation electrode, and the inion for the return electrode). Subjects will be randomized into two groups, one receiving a 10-day (5 days/week for 2 weeks) treatment with real cerebellar tACS and the other receiving a sham stimulation. The patient's motor function, cognitive function, sleep, mental state, plantar pressure, electroencephalogram, and magnetic resonance imaging will be assessed before and after the intervention.

There will be a total of 4 visits. All patients receiving CB-tACS will be visited face to face at baseline, day 1, day 30, and day 90 after the treatment begins.

• Study Type: Observational
• Enrollment (Anticipated): 164

Contacts and Locations

• Study Contact: Name: Shi-Rui Gan, MD, PhD; Phone Number: 86 0591-87982772; Email: ganshirui@fjmu.edu.cn

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350005
      • Recruiting
      • Department of Neurology, The First Affiliated Hospital Fujian Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Description

Inclusion Criteria:

• for SCA3

  • Patients with detectable clinical signs and confirmed genetic diagnosis with SCA3
  • SCA3 patients aged 18 - 80 years
  • Patients or their family members have informed consent to the study and signed relevant documents
  • The pre-study ataxia Assessment Score (SARA) ranged from 3 to 30

• for MSA-C

  • Aged 30-80 years
  • Diagnosed as clinically determined (Established)MSA-C or clinically Probable MSA-C according to the latest MSA diagnostic criteria
  • No more than 4 years after diagnosis of MSA-C
  • Able to walk independently or with assistance
  • Have a life expectancy of at least 3 years
  • Women of childbearing age with MSA need to use contraceptive measures

Exclusion Criteria:

1. Patients who have concomitant epilepsy.
2. Patients with a serious cognitive disorder, behavioral disorder, or mental illness
3. Patients with a history of seizures, stroke, encephalitis, or other degenerative neurological diseases

4. Patients with a serious medical disease

   • Patients who concomitantly suffer from severe renal impairment, convulsions, stomach ulcers, or moderate or more severe liver disease
   • Patients with uncontrolled high blood pressure or diabetes
5. History of head injury or neurosurgical interventions.
6. History of any metal in the head (outside the mouth).
7. Known history of any metallic particles in the eye, implanted cardiac pacemaker, implanted neurostimulators, surgical clips (above the shoulder line), or any medical pumps.
8. Patients who have taken other investigational products within 4 weeks before being enrolled in this clinical trial, or patients who are pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Real CB-tACS (10 days cerebellar tACS); Real cerebellar tACS, 70Hz,2mA (peak to peak), 40min/day (10s ramp up and 10s ramp down), (10 sessions, 5 days/week for 2 weeks)	Device: Transcranial Alternating Current Stimulation; Cerebellar Transcranial Alternating Current Stimulation（CB-tACS）
Sham CB-tACS (10 days sham cerebellar tACS); Sham cerebellar tACS,10Hz, 2mA (peak to peak) for 40s, and then no current 40min/day (10s ramp up and 10s ramp down), (10 sessions, 5 days/week for 2 weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Ataxia symptoms (Scale for the Assessment and Rating of Ataxia (SARA))	To compare the proportion of patients with SARA improvement (decrease) of at least 1.5 from baseline after 2 weeks, assessing changes in the SARA Score	Baseline - 2 weeks
Changes of Clinical Evaluation from UMSARS (Unified Multiple System Atrophy Rating Scale) (only for MSA-C)	UMSARS I: This is an assessment of daily life activities via 12 items scale used to assess language, writing, autonomy, walking, and the presence of possible urinary, sexual, or intestinal disorders. (0=no disorder, 48=severe) UMSARS II: Motor examination based on 14 items that evaluate particular facial expression, oculomotricity, oral expression, tremors, or walking. 0=no disorder, 56=severe disorders. UMSARS III: Blood pressure and heart rate measurements in lying and standing positions for 10 min every minute. UMSARS IV: Assessment of the disability from 1 to 5; 1 = completely independent; 5 = totally dependent. Changes of Clinical Evaluation for UMSARS improvement (decrease) from baseline to 2 weeks.	Baseline - 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the International Cooperative Ataxia Rating Scale (ICARS) Score From Baseline	ICARS: semi-quantitative 100-point scale, yielding a total score of 0 (no ataxia) to 100 (most severe ataxia)	Baseline - 2 weeks - 1 month - 3 months
Changes in the Scale for the Assessment and Rating of Ataxia (SARA) Score From Baseline	SARA: 8-item performance-based scale, yielding a total score of 0 (no ataxia) to 40 (most severe ataxia)	Baseline - 2 weeks - 1 month - 3 months
Changes in the 9 Hole Peg Test (9HPT) Score From Baseline	Three timed trials of 9HPT were performed and averaged (mean values are reported) for each separate hand (dominant and nondominant). The total time to complete the task will be recorded for each trial and each separate hand (dominant and nondominant). Longer times represent greater impairment.	Baseline - 2 weeks - 1 month - 3 months
Hand Grip Strength	Baseline - 2 weeks - 1 month - 3 months	This is a basic force measurement of hand grip with a dynamometer. Hand grip strength is measured using the Jamar Grip.
Pittsburgh Sleep Quality Index (PSQI)	The PSQI is the most commonly used instrument to assess the subjective sleep quality of adults in clinical and community settings.	Baseline - 2 weeks - 1 month - 3 months
Epworth score	The Epworth auto-questionnaire, rated from 0 (better) to 24 (worse), assesses day-time sleepiness.	Baseline - 2 weeks - 1 month - 3 months
Montreal Cognitive Assessment (MoCA）	In addressing cognitive screening tools, the MMSE and the MoCA are the most commonly used methods in detecting cognitive impairment detection in both clinical and research settings.	Baseline - 2 weeks - 1 month - 3 months
Mini-Mental State Examination (MMSE)	In addressing cognitive screening tools, the MMSE and the MoCA are the most commonly used methods in cognitive impairment detection in both clinical and research fields.	Baseline - 2 weeks - 1 month - 3 months
Hamilton Anxiety Scale (HAMA)	HAMA contains 14 questions; each question includes 5 items. Responses are scored as 0 (never), 1 (mild), 2 (moderate), 3 (severe), or 4 (extremely serious). The total score of HAMA is operationally categorized as follows: no anxiety (score 0-6), mild and moderate anxiety (score 7-13), and severe anxiety (score ≥ 14).	Baseline - 2 weeks - 1 month - 3 months
Hamilton Depression Scale (HAMD)	HAMD contains 17 questions; each question includes 5 items. Responses are scored as 0 (never), 1 (mild), 2 (moderate), 3 (severe), or 4 (extremely serious). The total score of HAMD can be classified into normal (score 0-6), mild and moderate (score 7-23), and severe depression (score ≥ 24).	Baseline - 2 weeks - 1 month - 3 months
Changes From Baseline in 5 Level EQ-5D (EQ-5D-5L)	The EQ-5D-5L is a standard measure of health-related quality of life. EQ-5D-5L consists of two components: a health state profile and a visual analog scale (VAS). EQ-5D health state profile comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. The 5D-5L systems are converted into a single index utility score between 0 to 1, where a higher score indicates a better health state. The VAS records the participant's health on a 0-100 mm VAS scale, with 0 indicating "the worst health you can imagine" and 100 indicating "the best health you can imagine." Higher scores of EQ-VAS indicate better health.	Baseline - 2 weeks - 1 month - 3 months
Multiple System Atrophy Quality of Life (MSA-QoL) Score	The score of other sub-dimension of the MSA Quality of Life scale. The MSA-QoL questionnaire is composed of three different subscales: motor (14 items), non-motor (12 items), and emotional/social (14 items). The response options for each question range from 0 (no problem) to 4 (extreme problem), with higher total scores reflecting more impaired quality of life. The MSA-QoL also includes a visual analog scale (VAS) of how satisfied patients feel (range 0-100, with lower scores indicating a lower quality of life).	Baseline - 2 weeks - 1 month - 3 months
Spatiotemporal dynamic changes measured with electroencephalography (EEG)	Changes in spatiotemporal dynamics in different frequency bands (theta, alpha, beta, gamma) will be assessed with high density-EEG after tACS intervention (gamma, sham)	Baseline - 2 weeks - 1 month - 3 months
Changes from temporospatial parameters of gait	Gait parameters measured by Multimodal Gait Analysis System. The kinetic and kinematic data of gait will be collected in the gait analysis corridor using two sets of smart insole systems and two sets of gyroscope sensor systems.	Baseline-2 weeks - 1 month - 3 months
Changes in Neuroimage changes in Magnetic Resonance Imaging (MRI)	Including T1, resting-state functional MRI, and Diffusional Kurtosis Imaging (DKI)	Baseline - 2 weeks - 1 month - 3 months

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Fujian Medical University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): March 31, 2023

Study Registration Dates

• First Submitted: September 24, 2022
• First Submitted That Met QC Criteria: September 24, 2022
• First Posted (Actual): September 28, 2022

Study Record Updates

• Last Update Posted (Actual): October 10, 2022
• Last Update Submitted That Met QC Criteria: October 6, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: effectiveness; Brain oscillations; tACS; SCA3; MSA-C
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; Cerebellar Diseases; Ataxia; Multiple System Atrophy; Shy-Drager Syndrome; Cerebellar Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations; Machado-Joseph Disease
• Other Study ID Numbers: MRCTA, ECFAH of FMU[2022]399

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No