## Protocol Section
### Identification Module
**NCT ID:** NCT06420271

**Acronym:** EtABeta

**Brief Title:** Effects of Cerebellar tACS-iTBS in Ataxia

**Official Title:** Effects of Combined Transcranial Electrical and Magnetic Stimulation of Cerebellum on Balance Function in Ataxia Patients

#### Organization Study ID Info
**ID:** 80/SL/23
#### Organization
**Class:** OTHER
**Full Name:** I.R.C.C.S. Fondazione Santa Lucia
### Status Module
#### Completion Date
**Date:** 2026-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-17

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-09-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-17
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** I.R.C.C.S. Fondazione Santa Lucia

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** 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.

### Conditions Module

**Conditions:**

- Ataxia

**Keywords:**

- Non Invasive Brain Stimulation

- Transcranial Magnetic Stimulation

- Intermittent Theta Burst Stimulation

- Transcranial Electrical Stimulation

- Transcranial Alternating Current Stimulation

- Exergaming

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

**Intervention Model Description:** A randomized cross-over design will be used. A 3-weeks wash-out period will be observed between the two conditions (real and sham).

##### Masking Info

**Masking:** TRIPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 30

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 10 sessions of real 5Hz tACS with real iTBS + exergaming biofeedback, 5 times per weeks for two weeks.

**Intervention Names:**

- Device: Real (real iTBS/tACS + exergaming)

**Label:** Real

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 10 sessions of sham 5Hz tACS with sham iTBS + exergaming biofeedback, 5 times per weeks for two weeks.

**Intervention Names:**

- Device: Sham (sham iTBS/tACS + exergaming)

**Label:** Sham

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Real

**Description:** 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. 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): 1) latero-lateral load shift; 2) antero posterior load shift; 3) omnidirectional displacement (combined latero-lateral and antero-posterior loading).

**Name:** Real (real iTBS/tACS + exergaming)

**Other Names:**

- real iTBS/tACS + exergaming

**Type:** DEVICE

#### Intervention 2

**Arm Group Labels:**

- Sham

**Description:** 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. 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): 1) latero-lateral load shift; 2) antero posterior load shift; 3) omnidirectional displacement (combined latero-lateral and antero-posterior loading).

**Name:** Sham (sham iTBS/tACS + exergaming)

**Other Names:**

- sham iTBS/tACS + exergaming

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** 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)

**Description:** MICARS was developed to quantify the level of impairment as a result of ataxia as related to hereditary ataxias. Score ranges from 0 to 120 where 120 indicates severe ataxia.

**Measure:** Changes in the Modified International Cooperative Ataxia Rating Scale (MICARS)

**Time Frame:** Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)

#### Secondary Outcomes

**Description:** 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.

**Measure:** 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)

**Description:** 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.

**Measure:** Changes in postural control

**Time Frame:** Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)

**Description:** 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.

**Measure:** Changes in cortico-spinal excitability

**Time Frame:** Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)

**Description:** 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, 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.

**Measure:** Change in Cerebellar Brain Inibition (CBI)

**Time Frame:** Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)

### Eligibility Module

**Eligibility Criteria:** 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.

**Maximum Age:** 80 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** g.koch@hsantalucia.it

**Name:** Giacomo Koch, Prof.

**Phone:** 0651501181

**Role:** CONTACT

**Contact 2:**

**Email:** v.pezzopane@hsantalucia.it

**Name:** Valentina Pezzopane, MSc

**Phone:** 0651501181

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** University of Roma La Sapienza

**Name:** Danny Spampinato, PhD

**Role:** STUDY_CHAIR

**Official 2:**

**Affiliation:** IRCCS Santa Lucia Foundation

**Name:** Alex Martino Cinnera, PhD

**Role:** STUDY_CHAIR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Spampinato D, Avci E, Rothwell J, Rocchi L. Frequency-dependent modulation of cerebellar excitability during the application of non-invasive alternating current stimulation. Brain Stimul. 2021 Mar-Apr;14(2):277-283. doi: 10.1016/j.brs.2021.01.007. Epub 2021 Jan 20.

**PMID:** 33482375

**Citation:** Libri I, Cantoni V, Benussi A, Rivolta J, Ferrari C, Fancellu R, Synofzik M, Alberici A, Padovani A, Borroni B. Comparing Cerebellar tDCS and Cerebellar tACS in Neurodegenerative Ataxias Using Wearable Sensors: A Randomized, Double-Blind, Sham-Controlled, Triple-Crossover Trial. Cerebellum. 2024 Apr;23(2):570-578. doi: 10.1007/s12311-023-01578-6. Epub 2023 Jun 22.

**PMID:** 37349632

**Citation:** Guerra A, Suppa A, Bologna M, D'Onofrio V, Bianchini E, Brown P, Di Lazzaro V, Berardelli A. Boosting the LTP-like plasticity effect of intermittent theta-burst stimulation using gamma transcranial alternating current stimulation. Brain Stimul. 2018 Jul-Aug;11(4):734-742. doi: 10.1016/j.brs.2018.03.015. Epub 2018 Mar 24.

**PMID:** 29615367

**Citation:** Gong C, Long Y, Peng XM, Hu H, Chen J, Xiao L, Zhong YB, Wang MY, Luo Y. Efficacy and safety of noninvasive brain stimulation for patients with cerebellar ataxia: a systematic review and meta-analysis of randomized controlled trials. J Neurol. 2023 Oct;270(10):4782-4799. doi: 10.1007/s00415-023-11799-8. Epub 2023 Jul 17.

**PMID:** 37460852

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020820

- Term: Dyskinesias

- ID: D000009461

- Term: Neurologic Manifestations

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000002526

- Term: Cerebellar Diseases

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M4565

- Name: Ataxia

- Relevance: HIGH

- As Found: Ataxia

- ID: M5773

- Name: Cerebellar Ataxia

- Relevance: HIGH

- As Found: Ataxia

- ID: M22574

- Name: Dyskinesias

- Relevance: LOW

- As Found: Unknown

- ID: M12404

- Name: Neurologic Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: M5775

- Name: Cerebellar Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000001259

- Term: Ataxia

- ID: D000002524

- Term: Cerebellar Ataxia

### Intervention Browse Module - Browse Branches

- Abbrev: Infl

- Name: Anti-Inflammatory Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M16974

- Name: Triamcinolone

- Relevance: LOW

- As Found: Unknown

- ID: M16975

- Name: Triamcinolone Acetonide

- Relevance: LOW

- As Found: Unknown

- ID: M237966

- Name: Triamcinolone hexacetonide

- Relevance: LOW

- As Found: Unknown

- ID: M209573

- Name: Triamcinolone diacetate

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
