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

NCT ID: NCT07114809

Last Updated: 2025-08-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-02

Study Completion Date

2026-01-31

Brief Summary

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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.

Detailed Description

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To achieve our aims, we planned a double-blind, randomized, prospective, controlled study. To this purpose, we will recruit 80 MS subjects affected by cognitive impairment (CI). Patients will be selected from outpatients attending the Department of Neurology of ASL3 Genoa and the Neurorehabilitation unit of IRCCS Ospedale Policlinico San Martino, Genoa. The participants will be randomly assigned to two groups, 40 in the experimental group (EG), 40 in the control group (CG), matched for demographic data (gender, age), EDSS and disease duration. All subjects will undergo a cognitive training by means of the exergames system (10 sessions, one hour per session, 5 days per week, for two consecutive weeks). Patients in the EG group will undergo a simultaneous A-tDCS over the left DLFPC, while CG will receive a S-tDCS over the same area. The tDCS will be delivered by a battery-driven, constant current simulator with a LCD touch screen (HDC progr), a portable stimulator (HDC stim), 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 .

In addition, in tasks where a cognitive conflict arises, the DLPFC contributes to increased cognitive control through its connections with the anterior cingulate cortex . Finally A-tDCS of the DLPFC has been shown to enhance working memory and executive function in healthy subjects as well as in PwMS . An electroconductive gel will be applied under the electrodes in order to reduce contact impedance. Impedance will be constantly kept below 5 kOhm. Only the tDCS investigators will be aware of the type of stimulation, while the patients and the neuropsychological assessors will be blind as to the nature of the project. During the exergames 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 . In the StDCS session (20 minutes) 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 (anodic) stimulation. Doing this, all the subjects will be blinded on the type of stimulation (anodal or sham). All the patients will participate to the cognitive training by means of exergames, which includes motor and cognitive tasks that incorporate enjoyment, technology, and health care.

Conditions

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Cognitive Impairment Multiple Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

double blind, randomized, controlled trial
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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

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

Group Type EXPERIMENTAL

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

Intervention Type 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.

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

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

Group Type SHAM_COMPARATOR

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

Intervention Type 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.

Interventions

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

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.

Intervention Type DEVICE

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

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.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. MS diagnosis according to McDonald's criteria (McDonald 2017);
2. 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).

Exclusion Criteria

1. subjects affected by major psychiatric disorders
2. epilepsy
3. previous brain surgery
4. MS relapse requiring steroid therapy in the previous two months
5. bilateral visual acuity \< 6/10
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Italian Multiple Sclerosis Foundation

OTHER

Sponsor Role collaborator

Ospedale Policlinico San Martino

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Laura Mori, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Ospedale Policlinico San Martino IRCCS

Locations

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Azienda Sanitaria Genovese

Genova, Italy, Italy

Site Status RECRUITING

Ospedale Policlinico San Martino - IRCCS

Genova, Italy, Italy

Site Status RECRUITING

Italian multiple sclerosis foundation

Genova, Italy, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Laura Mori, MD, PhD

Role: CONTACT

*39 010 555 5645

Lucilla Vestito, ST, PhD

Role: CONTACT

+39 010 353 7038

Facility Contacts

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Fabio Bandini, MD

Role: primary

*39 010 8491

Laura Mori, MD, PhD

Role: primary

*39 010 555 5645

Lucilla Vestito, ST, PhD

Role: backup

*39 010 353 7038

Giampaolo Brichetto, MD, PhD

Role: primary

+39 010 469 5886

References

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Other Identifiers

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2022/R-Multi/034

Identifier Type: -

Identifier Source: org_study_id

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