Effects of Cerebellar tACS-iTBS in Ataxia (EtABeta)

February 12, 2026 updated by: I.R.C.C.S. Fondazione Santa Lucia

Effects of Combined Transcranial Electrical and Magnetic Stimulation of Cerebellum on Balance Function in Ataxia Patients

Ataxia refers to a group of neurological disorders characterized by impaired coordination and balance due to dysfunction in the cerebellum or its connections. Traditional therapeutic approaches for ataxia have shown limited efficacy, prompting researchers to explore alternative interventions. Non-invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and intermittent theta burst stimulation (iTBS), have emerged as potential therapeutic options. The aim of this study is to investigate the combined effect of tACS-iTBS on balance functions in ataxia disorders.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Ataxia comprises a heterogeneous group of acquired or inherited disorders primarily involving cerebellar dysfunction, leading to impaired coordination and motor learning. Traditional treatments, including medication and physical therapy, often provide limited symptomatic improvement. Non-invasive brain stimulation (NIBS) techniques have emerged as promising tools for modulating cerebellar activity and enhancing motor function. Transcranial magnetic stimulation (TMS) can influence cortical excitability and plasticity, and studies have shown that high-frequency cerebellar rTMS can improve motor performance in spinocerebellar ataxia. Intermittent theta burst stimulation (iTBS), a patterned form of TMS, has demonstrated benefits in other movement disorders, suggesting potential applicability to ataxia. Transcranial direct current stimulation (tDCS), which modulates neuronal excitability via weak electrical currents, has shown improvements in static and dynamic balance in degenerative cerebellar ataxia. Transcranial alternating current stimulation (tACS) modulates neural oscillations and early studies indicate possible benefits for ataxia symptoms. Recent work has explored combining NIBS modalities to enhance neuromodulatory effects. In preliminary experiments, combined cerebellar tACS and iTBS increased MEP amplitudes more than iTBS alone, with effects lasting up to 30 minutes. These synergistic effects may translate into improved motor performance, coordination, and balance. The present study aims to investigate whether combining real or sham tACS with iTBS produces greater benefits than exergaming biofeedback alone in individuals with ataxia. A cross-over design will be used so that each participant serves as their own control. The primary outcomes will include motor coordination, balance, and cerebello-cortical plasticity. The rationale is that tACS may optimize oscillatory activity while iTBS enhances excitability, thereby jointly promoting neuroplasticity in cerebellar networks. The study will recruit individuals diagnosed with ataxia and assess the therapeutic potential of combined NIBS interventions.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Italy
    • Lazio
      • Rome, Lazio, Italy, 00179
        • Recruiting
        • IRCCS Santa Lucia Foundation
        • Contact:
          • Phone Number: 0651501181

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Confirmed diagnosis of ataxia based on clinical assessment and/or neuroimaging findings.
  2. Stable medication regimen for at least four weeks prior to the study.
  3. Sufficient cognitive ability to understand and comply with study instructions.

Exclusion Criteria:

  1. History of seizures.
  2. Severe general impairment or concomitant diseases.
  3. Intracranial metal implants.
  4. Cardiac pacemaker.
  5. Pregnancy status.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Real tACS + real iTBS + exergaming
10 sessions of real 5Hz tACS with real iTBS + exergaming biofeedback, 5 times per weeks for two weeks.
Device: Real (real iTBS/tACS + exergaming)
Stimulation will be applied to the cerebellum. The tACS session duration will be 190 seconds with a frequency of 5 Hz coupled with iTBS (coil positioned tangentially with respect to the scalp)(600 pulses consisting of bursts of 3 stimuli at 50 Hz, repeated at intervals of 200ms, with an intensity of 80% of active motor threshold -AMT-) (Huang et al., 2005) for a total duration of 190 seconds (repeated over both cerebellar hemispheres after a 15-minute rest period). The exergaming will be performed with an adaptive system, comprising a force platform connected to a computer. The system is designed to enhance standard balance rehabilitation programs by guiding the user's performance of prescribed physical exercises through a video interface. Patients will perform 3 different exercises (10 minutes of training for a total of 30 minutes): latero-lateral and antero posterior load shift, omnidirectional displacement (combined latero-lateral and antero-posterior loading).
Other Names:
  • real iTBS/tACS + exergaming
Placebo Comparator: Sham tACS + sham iTBS + exergaming
10 sessions of sham 5Hz tACS with sham iTBS + exergaming biofeedback, 5 times per weeks for two weeks.
Device: Sham (sham iTBS/tACS + exergaming)
Stimulation will be applied to the cerebellum. The tACS session duration will be 10 seconds with a frequency of 5 Hz coupled with sham iTBS (coil positioned perpendicularly with respect to the scalp)(600 pulses consisting of bursts of 3 stimuli at 50 Hz, repeated at intervals of 200ms, with an intensity of 80% of active motor threshold -AMT-) (Huang et al., 2005) for a total duration of 190 seconds (repeated over both cerebellar hemispheres after a 15-minute rest period). The exergaming will be performed with an adaptive system, comprising a force platform connected to a computer. The system is designed to enhance standard balance rehabilitation programs by guiding the user's performance of prescribed physical exercises through a video interface. Patients will perform 3 different exercises (10 minutes of training for a total of 30 minutes): latero-lateral and antero posterior load shift, omnidirectional displacement (combined latero-lateral and antero-posterior loading).
Other Names:
  • sham iTBS/tACS + exergaming

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes in the International Cooperative Ataxia Rating Scale (ICARS)
Time Frame: Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)
ICARS was developed to quantify the level of impairment as a result of ataxia as related to hereditary ataxias. Score ranges from 0 to 100 where 100 indicates severe ataxia.
Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in the Scale for the Assessment and Rating of Ataxia (SARA)
Time Frame: Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)
SARA is a clinical scale developed to assess a range of different impairments in cerebellar ataxia. The scale is made up of 8 items related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements and heel-shin test. Score ranges from 0 to 40 where 40 indicates severe ataxia.
Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)
Changes in the Short Form-36 Health Survey (SF-36)
Time Frame: Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)
SF-36 is an outcome measure instrument that is often used, well-researched, self-reported measure of health. Scores range from 0 to 100 for each domain, where 100 indicates a more favorable health-state.
Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)
Changes in postural control
Time Frame: Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)
Instrumented postural stability will be assessed using a 75 cm (length x width) static force platform (PlatformBPM 120, Physical Support Italia, Italy). The signals will be amplified and acquired using dedicated software (Physical Gait Software Vv. 2.66, Physical SupportItalia, Italy). The length of the center of pressure (CoP) trajectory (mm) will be measured as indicator of the postural stability. An increase in the length of CoP indicates a severe impairment in postural control.
Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)
Changes in cortico-spinal excitability
Time Frame: Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)
Twenty Motor evoked potentials (MEPs) will be collected from left and right primary motor cortex with single pulses of transcranial magnetic stimulation (TMS) set at 1 mV. An increase in the MEPs amplitude indicates an improvement in cortico-spinal activity recorded from the first dorsal interosseous and tibialis anterior muscles.
Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Cerebellar Brain Inhibition (CBI)
Time Frame: Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)
CBI will be performed with two Magstim figure-of-eight coils (70 mm diameter), one placed over the primary motor cortex and the other centered over the contralateral cerebellar hemisphere, 1 cm below and 3 cm lateral to the Inion with an upward current induced to the brain. For each CBI evaluation, we will record 20 TMS test stimuli (TS) over the M1 that were set at intensity to elicit an MEP ∼1 mV. In half of these trials, selected randomly, a TMS conditioning stimulus (CS) was delivered over the contralateral cerebellar hemisphere 5 ms prior to the TS at an intensity of 120% of the resting motor threshold (RMT). Thus, a total of 20 TS and 20 CS + TS pulses will be administered. CBI will be calculated as the ratio of the mean MEP amplitude in the CS + TS relative to TS. An increase in CBI indicates higher connectivity between the cerebellum and primary motor cortex.
Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
I.R.C.C.S. Fondazione Santa Lucia

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Danny Spampinato, PhD, University of Roma La Sapienza
  • Study Chair: Alex Martino Cinnera, PhD, IRCCS Santa Lucia Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 14, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 17, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 20, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 12, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 80/SL/23

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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