Effects of Cerebellar tACS-iTBS in Ataxia

Ataxia Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06420271
• Other study ID #: 80/SL/23
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2024
• Source: I.R.C.C.S. Fondazione Santa Lucia
• Contact: Giacomo Koch, Prof.
• Phone: 0651501181
• Email: g.koch[@]hsantalucia.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: December 31, 2026
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia

Intervention

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. 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).
• 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. 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).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
I.R.C.C.S. Fondazione Santa Lucia

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the Scale for the Assessment and Rating of Ataxia (SARA)	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)
Primary	Changes in the Modified International Cooperative Ataxia Rating Scale (MICARS)	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.	Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)
Secondary	Changes in the Short Form-36 Health Survey (SF-36)	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)
Secondary	Changes in postural control	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)
Secondary	Changes in cortico-spinal excitability	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.	Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)
Secondary	Change in Cerebellar Brain Inibition (CBI)	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.	Baseline (1), 2 weeks from baseline (1), Baseline (2), 2 weeks from baseline (2)