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

Not Applicable

Recruiting

• Conditions: Cognitive Impairment; Multiple Sclerosis

• Registration Number: NCT07114809
• Lead Sponsor: Ospedale Policlinico San Martino

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.

Detailed Description

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.

Study Timeline

• Study Start: 2024-09-02
• Status Verified: 2025-08
• Study First Submitted: 2025-08-04
• Study First Submitted QC: 2025-08-04
• Last Update Submitted: 2025-08-04
• Study First Posted: 2025-08-11
• Last Update Posted: 2025-08-11
• Primary Completion: 2026-01
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Revised Brief Visuo-Spatial Memory test (BVMT-R)	The patients will be evaluated at baseline, up to two weeks, one month and six months later	Part of the BICAMS test. minimum score 0 (poor performance) maximum score 12 (normal performance)
California Verbal Learning test II edition (CVLT-II)	The patients will be evaluated at baseline, up to two weeks, one month and six months later	Part of the BICAMS test. Minimum score 0 (poor performance), maximum score 80 (normal performance)
Paced Auditory Serial Addition Task 3" and 2" intervals (PASAT)	The patients will be evaluated at baseline, up to two weeks, one month and six months later	A neuropsychological test widely utilized for the cognitive assessment in PwMS. Minimum score 0 (poor performance) maximum score 60 (normal performance)
Symbol digit modalities test (SDMT)	The patients will be evaluated at baseline, up to two weeks, one month and six months later.	Part of the BICAMS test. minimum score 0 (poor performance), maximum score 120 (normal performance)

Secondary Outcome Measures

Name	Time	Method
Multiple Sclerosis Quality of life (MSQoL)	The patients will be evaluated at baseline, up to two weeks, one month and six months later	Self-reported measures of quality of life in people with Multiple Sclerosis. Minimum score 0 (poor performance), Maximum score 100 (normal performance)
Beck depression inventory scale (BDI)	The patients will be evaluated at baseline, up to two weeks, one month and six months later	Self-reported measures of mood (depression). Minimum score 0 (poor performance), maximum score 63 (normal performance)
Fatigue Severity Scale (FSS)	The patients will be evaluated at baseline, up to two weeks, one month and six months later	Self-reported measures of fatigue in people with Multiple Sclerosis. Minimum score 9, maximum score 63. (Mean score ≥ 4: indicative of clinically significant fatigue. Mean score \< 4: fatigue not considered clinically significant.)

Trial Locations

Locations (3)

Azienda Sanitaria Genovese; 🇮🇹 Genova, Italy

Ospedale Policlinico San Martino - IRCCS; 🇮🇹 Genova, Italy

Italian multiple sclerosis foundation; 🇮🇹 Genova, Italy