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

Spinocerebellar Ataxia Type 3 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05557786
• Other study ID #: MRCTA, ECFAH of FMU[2022]399
• Status: Recruiting
• Start date: August 1, 2022
• Est. completion date: March 31, 2023

Study information

• Verified date: October 2022
• Source: First Affiliated Hospital of Fujian Medical University
• Contact: Shi-Rui Gan, MD, PhD
• Phone: 0591-87982772
• Email: ganshirui[@]fjmu.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 164
• Est. completion date: March 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia
• Machado-Joseph Disease
• Multiple System Atrophy
• Shy-Drager Syndrome
• Spinocerebellar Ataxia Type 3
• Spinocerebellar Ataxias
• Spinocerebellar Degenerations

Intervention

Device:
• Transcranial Alternating Current Stimulation
Cerebellar Transcranial Alternating Current Stimulation(CB-tACS)

Locations

Country	Name	City	State
China	Department of Neurology, The First Affiliated Hospital Fujian Medical University	Fuzhou	Fujian

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital of Fujian Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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
Secondary	Epworth score	The Epworth auto-questionnaire, rated from 0 (better) to 24 (worse), assesses day-time sleepiness.	Baseline - 2 weeks - 1 month - 3 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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