Impact of Anodal tDCS and Virtual Reality on Cognitive Dysfunction in Patients With Multiple Sclerosis

NCT07114809 | Recruiting DMC

• 1 other identifier: 2022/R-Multi/034
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

Brief Summary

Cognitive impairment (CI) affects a large amount of patients with Multiple Sclerosis (PwMS) even in the early stages of the disease, increasing the perception of fatigue and compromising the quality of life. Different restorative interventions have been tried in order to alleviate CI, but with limited efficacy . Transcranial direct current stimulation (tDCS), represents a very promising alternative, or add-on, to the traditional rehabilitative approaches in MS. Notably, other novel technologies, such as Virtual Reality (VR) and Exergame, are emerging as a reinforcing tool to the rehabilitative treatment of PwMS. tDCS and VR can be combined in protocols aimed at achieving a better therapeutic benefit across different neurological diseases (Cassani 2020). The aim of our project is to explore the potential benefits of the simultaneous application of AtDCS and VR in the rehabilitation of cognitive impairment of PwMS. The VR approach will be implemented with a non-immersive VR system (exergames). As a secondary outcome, we wish to verify whether our protocol may extend its benefits over 6 months. Eighty PwMs with CI will be consecutively enrolled. Their cognitive status will be assessed by a neuropsychological battery: the Brief International Cognitive Assessment for MS and the Paced Auditory Serial Addition Test. To be considered cognitively impaired one has to abnormally score on at least two tests. Forty patients will be randomized to the experimental group (EG) or to the control group (CG). All the patients will undergo rehabilitative treatment with exergame (10 sessions for two consecutive weeks, 5 days per week). The EG patients will undergo a concurrent A-tDCS over the left dorsolateral prefrontal cortex, while the CG will receive a sham stimulation (S-tDCS). The patients will be evaluated at baseline, at the end of the treatment, one month and six months later. The statistical analyses will be done using repeated-measures ANOVA. Expected results: we hypothesize that the cognitive performances of both EG and CG groups will show an improvement in the cognitive performances. We will expect, however, a significative difference between the two groups, with patients in the EG group demonstrating better results than the CG group. Finally, we hypothesize the beneficial effects in EG patients will last at least one month after the end of the experiment.

Conditions

Cognitive Impairment; Multiple Sclerosis

Keywords

Cognitive impairment; Multiple Sclerosis; Exergaiming; Virtual Reality; tDCS

Outcome Measures

Primary Outcomes (4)

• Revised Brief Visuo-Spatial Memory test (BVMT-R)

  Part of the BICAMS test. minimum score 0 (poor performance) maximum score 12 (normal performance)

  The patients will be evaluated at baseline, up to two weeks, one month and six months later

• Symbol digit modalities test (SDMT)

  Part of the BICAMS test. minimum score 0 (poor performance), maximum score 120 (normal performance)

  The patients will be evaluated at baseline, up to two weeks, one month and six months later.

• California Verbal Learning test II edition (CVLT-II)

  Part of the BICAMS test. Minimum score 0 (poor performance), maximum score 80 (normal performance)

  The patients will be evaluated at baseline, up to two weeks, one month and six months later

• Paced Auditory Serial Addition Task 3" and 2" intervals (PASAT)

  A neuropsychological test widely utilized for the cognitive assessment in PwMS. Minimum score 0 (poor performance) maximum score 60 (normal performance)

  The patients will be evaluated at baseline, up to two weeks, one month and six months later

Secondary Outcomes (3)

• Multiple Sclerosis Quality of life (MSQoL)

  The patients will be evaluated at baseline, up to two weeks, one month and six months later

• Beck depression inventory scale (BDI)

  The patients will be evaluated at baseline, up to two weeks, one month and six months later

• Fatigue Severity Scale (FSS)

  The patients will be evaluated at baseline, up to two weeks, one month and six months later

Study Arms (2)

Experimental group (EG) performing Anodal-tDCS (A-tDCS) and VR

EXPERIMENTAL

EG subjects will undergo a rehabilitative treatment with exergame and concurrent A-tDCS over the left dorsolateral prefrontal cortex.

Device: Experimental group (EG) performing Anodal-tDCS (A-tDCS) and VR

Control group (CG) performing sham-tDCS (S-tCDS) and VR

SHAM COMPARATOR

CG subjects will undergo a rehabilitative treatment with exergame and concurrent S-tDCS over the left dorsolateral prefrontal cortex.

Device: Sham Comparator: Control group (CG) performing sham-tDCS (S-tCDS) and VR

Interventions

Experimental group (EG) performing Anodal-tDCS (A-tDCS) and VR DEVICE

Patients in the EG group will undergo a simultaneous A-tDCS over the left DLFPC. The tDCS will be delivered by a battery-driven, constant current simulator, two holding bags of plant cellulose (7x5 cm) and two electrodes of conductive silicone. The active (anodal) electrode will be placed by means of a cap on the scalp overlying the left DLPFC (46 Brodmann Area). The reference electrode will be located over the right shoulder. The choice of the left DLPFC as the site of stimulation relies upon the evidence that this region has a critical role in the "top-down" control of the task-relevant stimuli processing (Miller 2001).The DLPFC contributes to increase cognitive control through its connections with the anterior cingulate cortex and has been shown to enhance working memory and executive function. During the cognitive training (on-line procedure), A-tDCS (current of 1,5 mA) will be delivered for 20 minutes, while maintaining the current density (0.06 mA/cm2) below the safety limits.

Experimental group (EG) performing Anodal-tDCS (A-tDCS) and VR

Sham Comparator: Control group (CG) performing sham-tDCS (S-tCDS) and VR DEVICE

CG will receive a S-tDCS over the DLPFC. In the S-tDCS session, the current will be turned off 30 sec after the beginning of the stimulation and turned on for the last 30 sec. By doing this, the patient feels an itching sensation below the electrodes at the beginning and at the end of stimulation, making this condition indistinguishable from the real A-tDCS stimulation. Doing this, all the subjects will be blinded on the type of stimulation. As well as in the EG, CG performs cognitive training including motor and cognitive exergames that incorporate enjoyment, technology, and health care.

Control group (CG) performing sham-tDCS (S-tCDS) and VR

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• MS diagnosis according to McDonald's criteria (McDonald 2017);
• age between 18 and 60 (to avoid participants with possible CI due to aging); 3) disability score ≤7.5 at the Expanded Disability Status Scale (EDSS, Kurtzke 1983).

You may not qualify if:

• subjects affected by major psychiatric disorders
• epilepsy
• previous brain surgery
• MS relapse requiring steroid therapy in the previous two months
• bilateral visual acuity \< 6/10

Sponsors & Collaborators

• Ospedale Policlinico San Martino: lead
• Italian Multiple Sclerosis Foundation: collaborator

Study Sites (3)

Azienda Sanitaria Genovese

Genova, Italy, 16100, Italy

RECRUITING

Ospedale Policlinico San Martino - IRCCS

Genova, Italy, 16132, Italy

RECRUITING

Italian multiple sclerosis foundation

Genova, Italy, 16149, Italy

RECRUITING

Related Publications (21)

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MeSH Terms

Conditions

Cognitive Dysfunction; Multiple Sclerosis

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Laura Mori, MD, PhD

  Ospedale Policlinico San Martino IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Mori, MD, PhD

CONTACT

*39 010 555 5645; laura.mori@hsanmartino.it

Lucilla Vestito, ST, PhD

CONTACT

+39 010 353 7038; lucilla.vestito@hsanmartino.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: double blind, randomized, controlled trial

Study Record Dates

• First Submitted: August 4, 2025
• First Posted: August 11, 2025
• Study Start: September 2, 2024
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3)