An interventional study of Experimental group (EG) performing Anodal-tDCS (A-tDCS) and VR and Sham Comparator: Control group (CG) performing sham-tDCS (S-tCDS) and VR in Cognitive Impairment and Multiple Sclerosis, sponsored by Ospedale Policlinico San Martino. Recruiting at 3 sites in Italy. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-08-11.
Sponsored by Ospedale Policlinico San Martino · Not applicable, Interventional, and Treatment
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.
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.
3,872 studies on the registry are indexed under Cognitive Dysfunction; 1,119 are open to participants now.
This study's planned enrollment of 80 is above the median of 64 across 2,794 interventional studies indexed under Cognitive Dysfunction.
Browse Cognitive Dysfunction studies →Ospedale Policlinico San Martino is the lead sponsor of 30 studies on the registry; 11 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
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Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
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Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
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.
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.
Revised Brief Visuo-Spatial Memory test (BVMT-R)
Part of the BICAMS test. minimum score 0 (poor performance) maximum score 12 (normal performance)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: The patients will be evaluated at baseline, up to two weeks, one month and six months later
Multiple Sclerosis Quality of life (MSQoL)
Self-reported measures of quality of life in people with Multiple Sclerosis. Minimum score 0 (poor performance), Maximum score 100 (normal performance)
Time frame: The patients will be evaluated at baseline, up to two weeks, one month and six months later
Beck depression inventory scale (BDI)
Self-reported measures of mood (depression). Minimum score 0 (poor performance), maximum score 63 (normal performance)
Time frame: The patients will be evaluated at baseline, up to two weeks, one month and six months later
Fatigue Severity Scale (FSS)
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.)
Time frame: The patients will be evaluated at baseline, up to two weeks, one month and six months later
Plan to share: No — At this time, individual participant data (IPD) will not be shared due to concerns regarding patient confidentiality and the challenges of fully anonymizing sensitive clinical and neuropsychological data. In addition, data sharing is not currently covered by participant informed consent and would require additional ethical and regulatory approvals to ensure compliance with privacy laws and institutional policies.
Started Sep 2024 (actual). Primary completion is estimated for Jan 2026, 16 months after the start.
Of 1,442 non-industry interventional studies with no phase under Cognitive Dysfunction, half reached primary completion within 27 months of starting (the median), counting those still running; a quarter within 13 and three quarters within 51. This study's planned 16 months is below that.
Counting every sponsor, half of 1,511 studies reached it within 27 months; a quarter within 12 and three quarters within 50.
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