Clinical trial NCT06821256: Efficacy and Safety of Transcranial dIrect Current stiMulation in Multiple System Atrophy-Cerebellar Variant
Official title: Efficacy and Safety of Transcranial dIrect Current stiMulation (tDCS) on Cerebellar Symptoms in Multiple System Atrophy-Cerebellar Variant (MSA-C) (STIM-MSA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Multiple System Atrophy - Cerebellar Subtype (MSA-C)
Keywords: Multiple System Atrophy type C (MSA-C),
Transcranial direct current stimulation (tDCS)
Lead sponsor: University of Salerno
Sponsor class: OTHER
First posted: 2025-02-11
Enrollment: 30
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Patients will be randomly assigned to one of the two arms and all will receive a sham-stimulation for 5 consecutive days/week (i.e.,Monday to Friday) and an active stimulation for 5 consecutive days/week (i.e., Monday to Friday). The order of the sham- vs active-stimulation will be also randomized within each arm. The active stimulation will consist of an anodal stimulation over the cerebellum area (2 cm under the inion, using a 7 × 5 cm sponge electrode), with the cathode being applied either to the right deltoid muscle (arm 1: cerebellar stimulation) or over the spinal lumbar enlargement (2 cm under T11; arm 2: cerebellar-spinal stimulation) using a sponge electrode of the same size as the anode. During anodal stimulation, a constant current of 2 mA will be applied for 20 minutes, as suggested by recently published consensus recommendations (Grimaldi et al, 2014). For the sham condition, the electrode placement will be the same as for the active stimulation, but the electric current
Primary purpose: TREATMENT

Brief summary: This is a double-blind, randomized, sham-controlled clinical trial that aim to verify the safety and the efficacy of anodal transcranial direct current stimulation (tDCS) cerebellar symptoms in Multiple System Atrophy type C (MSA).

Detailed description: Multiple system atrophy (MSA) is a progressive neurodegenerative disease for which, to date, no causal therapy is available, symptomatic treatment therefore playing a pivotal role in patient care (Fanciulli \& Wenning, 2015). Unfortunately, there are very limited effective symptomatic treatments, especially for the cerebellar variant of MSA (MSA-C) which calls for the urgent need of developing alternative strategies to improve patients' disability and quality of life (QoL). An emergent approach to cerebellar disorders of various etiologies stands in the use of non-invasive brain stimulation (NIBS) techniques (Erro R et al., 2017), namely in the use of trans-cranial direct current stimulation (tDCS), to modulates neuronal excitability in a polarity-specific manner by delivering prolonged (up to 20-30 min) but weak (1-2 mA) currents to brain tissues via electrodes placed on the scalp (Stagg \& Nitsche, 2011).

This project has been designed as a double-blinded, sham-controlled, cross-over trial with two independent arms to assess the feasibility and compare the efficacy of two different tDCS protocols. Sample size calculation has been calculated on preliminary unpublished results of our own research using tDCS in other atypical parkinsonisms (i.e., PSP) and we will accordingly recruit 15 patients for each arm of the study. Patients will be randomly assigned to one of the two arms and all will receive a sham-stimulation for 5 consecutive days/week (i.e.,Monday to Friday) and an active stimulation for 5 consecutive days/week (i.e., Monday to Friday). The order of the sham- vs active-stimulation will be also randomized within each arm. The active stimulation will consist of an anodal stimulation over the cerebellum area (2 cm under the inion, using a 7 × 5 cm sponge electrode), with the cathode being applied either to the right deltoid muscle (arm 1: cerebellar stimulation) or over the spinal lumbar enlargement (2 cm under T11; arm 2: cerebellar-spinal stimulation) using a sponge electrode of the same size as the anode. During anodal stimulation, a constant current of 2 mA will be applied for 20 minutes, as suggested by recently published consensus recommendations (Grimaldi et al, 2014). For the sham condition, the electrode placement will be the same as for the active stimulation, but the electric current will be ramped down 5 seconds after the beginning of the stimulation to make this condition indistinguishable from the experimental stimulation.

Before (T0), soon after the first week of the protocol (T1) and soon after the second week of the protocol (T2) all patients will be evaluated using 1) validated clinical scales for cerebellar disorders (SARA, ICARS) and 2) through the 8-m walking test (8MW); defined as the time needed to walk 8 m as quickly as possible but safely with any device but without the help of another person or wall. During the 8MW wearable sensors (OPAL) will be further used to collect objective measures of gait and balance. Finally, PROs will be collected by means of 1) the clinical global improvement measure (CGI-I) ranging from 1 (very much improved) to 7 (very much worse), with patients being asked to report their perceived improvement at T1 and T2; and 2) by two instruments for depicting change in QoL, namely the EuroQoL-5Dimensions, 3Levels (EQ-5D-3L) and the MSA-QoL (Schrag, Mov Disord 2007), both of which will be performed at T0, T1 and T2. Patients will be further asked whether they thought they were receiving real or sham stimulation at the end of the 2-week treatment.

Eligibility criteria: Inclusion Criteria:

* Multiple system atrophy cerebellar variant according with the Movemente Disorder Society criteria (Wenning et al 2022)
* Ability to walk either indipendently or with a minimum support

Exclusion Criteria:

* Presence of electrical stimulators (for example, pacemaker, Deep Brain Stimulation, DBS)
* Difficult in understanding Italian language
* Presence of severe sensory deficits (for example, visual or hearing impairments)
* History of drug abuse
* History of severe psychiatric disorders
* History of transient ischemic attacks
* Cortical or sub-cortical vascular lesions
* Seizures or severe heart problems and previous neurosurgical operations
* Pregnancy

Primary outcomes:
measure: Change from baseline to 1 week and two weeks follow in motor symptoms as assessed with sensor recordings (OPAL system)
timeFrame: Baseline (t0), at 1 week (t1), at 2 weeks (t2)
Secondary outcomes:
measure: Changing from baseline of measures from clinical scale (SARA)
timeFrame: Baseline (t0), at 1 week (t1), at 2 weeks (t2)
measure: Changing from baseline of measures from clinical scale (ICARS)
timeFrame: Baseline (t0), at 1 week (t1), at 2 weeks (t2)
measure: Changing from baseline of measures from clinical scale (UMSARS)
timeFrame: Baseline (t0), at 1 week (t1), at 2 weeks (t2)
measure: Changing from baseline of measures from patient related outcome
timeFrame: Baseline (t0), at 1 week (t1), at 2 weeks (t2)
measure: Changing from baseline of measures from patient related outcome
timeFrame: Baseline (t0), at 1 week (t1), at 2 weeks (t2)
Other outcomes:
Locations:
city: Salerno
country: Italy
facility: Centro per le Malattie Neurodegenerative (CEMAND) Dipartimento di Medicina e chirurgia, Sezione Neuroscienze, Università di Salerno
state: Sa
Study officials:
References:
citation: Stagg CJ, Nitsche MA. Physiological basis of transcranial direct current stimulation. Neuroscientist. 2011 Feb;17(1):37-53. doi: 10.1177/1073858410386614.
citation: Erro R, Antelmi E, Bhatia KP, Latorre A, Tinazzi M, Berardelli A, Rothwell JC, Rocchi L. Reversal of Temporal Discrimination in Cervical Dystonia after Low-Frequency Sensory Stimulation. Mov Disord. 2021 Mar;36(3):761-766. doi: 10.1002/mds.28369. Epub 2020 Nov 7.
citation: Erro R, Tinazzi M, Morgante F, Bhatia KP. Non-invasive brain stimulation for dystonia: therapeutic implications. Eur J Neurol. 2017 Oct;24(10):1228-e64. doi: 10.1111/ene.13363. Epub 2017 Aug 7.
citation: Datta A, Bansal V, Diaz J, Patel J, Reato D, Bikson M. Gyri-precise head model of transcranial direct current stimulation: improved spatial focality using a ring electrode versus conventional rectangular pad. Brain Stimul. 2009 Oct;2(4):201-7, 207.e1. doi: 10.1016/j.brs.2009.03.005.