Cognitive ImpairmenttDCScogNCT07114809
Impact of Anodal tDCS and Virtual Reality on Cognitive Dysfunction in Patients With Multiple Sclerosis
A study testing Experimental group (EG) performing Anodal-tDCS (A-tDCS) and VR in people with Cognitive Impairment and Multiple Sclerosis, run by Ospedale Policlinico San Martino at 3 sites in Italy.
Trial 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 . Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Cognitive Impairment, Multiple Sclerosis
- What is being tested?
- Experimental group (EG) performing Anodal-tDCS (A-tDCS) and VR
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 3 sitesItaly
- Study dates
- 2 Sep 2024to Jan 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy3 sites, 3 recruiting
- Recruiting
Azienda Sanitaria Genovese
Genova, Italy, 16100
Fabio Bandini, MD, *39 010 8491, fabio.bandini@asl3.liguria.it
- Recruiting
Ospedale Policlinico San Martino - IRCCS
Genova, Italy, 16132
Laura Mori, MD, PhD, *39 010 555 5645, laura.mori@hsanmartino.it
Lucilla Vestito, ST, PhD, *39 010 353 7038, lucilla.vestito@hsanmartino.it
- Recruiting
Italian multiple sclerosis foundation
Genova, Italy, 16149
Giampaolo Brichetto, MD, PhD, +39 010 469 5886, giampaolo.brichetto@aism.it
About this study
Official title: Impact of Anodal tDCS and Virtual Reality on Cognitive Dysfunction in Patients With Multiple Sclerosis: a Protocol of a Double Blind, Randomized, Prospective, Controlled Study.
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.
Read the 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.
- Conditions
- Cognitive Impairment, Multiple Sclerosis
- Being tested
- Experimental group (EG) performing Anodal-tDCS (A-tDCS) and VR, Sham Comparator: Control group (CG) performing sham-tDCS (S-tCDS) and VR
- Keywords
- Cognitive impairment, Multiple Sclerosis, Exergaiming, Virtual Reality, tDCS
- Medical subject headings
- Cognitive Dysfunction, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental group (EG) performing Anodal-tDCS (A-tDCS) and VRDevice
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.
Sham Comparator: Control group (CG) performing sham-tDCS (S-tCDS) and VRDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: Sham Comparator: Control group (CG) performing sham-tDCS (S-tCDS) and VR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Revised Brief Visuo-Spatial Memory test (BVMT-R)
Part of the BICAMS test. minimum score 0 (poor performance) maximum score 12 (normal performance)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Self-reported measures of quality of life in people with Multiple Sclerosis. Minimum score 0 (poor performance), Maximum score 100 (normal performance)
Measured: 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)
Measured: 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.)
Measured: The patients will be evaluated at baseline, up to two weeks, one month and six months later
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2025
- Study start2 Sep 2024
- Primary completionJan 2026 (estimated)
- Study completionJan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Cognitive ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double blind, randomized, controlled trial
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ospedale Policlinico San Martino
- Sponsor type
- University, hospital or other
- Collaborators
- Italian Multiple Sclerosis Foundation
- Responsible party
- Sponsor
- Investigators
- Laura Mori, MD, PhD, Principal investigator, Ospedale Policlinico San Martino IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07114809
- Sponsor's protocol ID
- 2022/R-Multi/034
- Acronym
- tDCScog
- Status last verified
- Aug 2025
- First submitted
- 4 Aug 2025
- Last updated
- 11 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Publications
Laver KE, George S, Thomas S, Deutsch JE, Crotty M. Virtual reality for stroke rehabilitation. Cochrane Database Syst Rev. 2015 Feb 12;2015(2):CD008349. doi: 10.1002/14651858.CD008349.pub3.
PubMed 25927099Cassani R, Novak GS, Falk TH, Oliveira AA. Virtual reality and non-invasive brain stimulation for rehabilitation applications: a systematic review. J Neuroeng Rehabil. 2020 Oct 31;17(1):147. doi: 10.1186/s12984-020-00780-5.
PubMed 33129331Solari A, Filippini G, Mendozzi L, Ghezzi A, Cifani S, Barbieri E, Baldini S, Salmaggi A, Mantia LL, Farinotti M, Caputo D, Mosconi P. Validation of Italian multiple sclerosis quality of life 54 questionnaire. J Neurol Neurosurg Psychiatry. 1999 Aug;67(2):158-62. doi: 10.1136/jnnp.67.2.158.
PubMed 10406981Poreisz C, Boros K, Antal A, Paulus W. Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res Bull. 2007 May 30;72(4-6):208-14. doi: 10.1016/j.brainresbull.2007.01.004. Epub 2007 Jan 24.
PubMed 17452283Charvet L, Shaw M, Dobbs B, Frontario A, Sherman K, Bikson M, Datta A, Krupp L, Zeinapour E, Kasschau M. Remotely Supervised Transcranial Direct Current Stimulation Increases the Benefit of At-Home Cognitive Training in Multiple Sclerosis. Neuromodulation. 2018 Jun;21(4):383-389. doi: 10.1111/ner.12583. Epub 2017 Feb 22.
PubMed 28225155Mattioli F, Bellomi F, Stampatori C, Capra R, Miniussi C. Neuroenhancement through cognitive training and anodal tDCS in multiple sclerosis. Mult Scler. 2016 Feb;22(2):222-30. doi: 10.1177/1352458515587597. Epub 2015 May 26.
PubMed 26014600Filippi M, Riccitelli G, Mattioli F, Capra R, Stampatori C, Pagani E, Valsasina P, Copetti M, Falini A, Comi G, Rocca MA. Multiple sclerosis: effects of cognitive rehabilitation on structural and functional MR imaging measures--an explorative study. Radiology. 2012 Mar;262(3):932-40. doi: 10.1148/radiol.11111299.
PubMed 22357892Mainero C, Caramia F, Pozzilli C, Pisani A, Pestalozza I, Borriello G, Bozzao L, Pantano P. fMRI evidence of brain reorganization during attention and memory tasks in multiple sclerosis. Neuroimage. 2004 Mar;21(3):858-67. doi: 10.1016/j.neuroimage.2003.10.004.
PubMed 15006652Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000 Sep 15;527 Pt 3(Pt 3):633-9. doi: 10.1111/j.1469-7793.2000.t01-1-00633.x.
PubMed 10990547Hiew S, Nguemeni C, Zeller D. Efficacy of transcranial direct current stimulation in people with multiple sclerosis: a review. Eur J Neurol. 2022 Feb;29(2):648-664. doi: 10.1111/ene.15163. Epub 2021 Nov 19.
PubMed 34725881Grigorescu C, Chalah MA, Lefaucheur JP, Kumpfel T, Padberg F, Ayache SS, Palm U. Effects of Transcranial Direct Current Stimulation on Information Processing Speed, Working Memory, Attention, and Social Cognition in Multiple Sclerosis. Front Neurol. 2020 Oct 15;11:545377. doi: 10.3389/fneur.2020.545377. eCollection 2020.
PubMed 33178103Nascimento AS, Fagundes CV, Mendes FADS, Leal JC. Effectiveness of Virtual Reality Rehabilitation in Persons with Multiple Sclerosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Mult Scler Relat Disord. 2021 Sep;54:103128. doi: 10.1016/j.msard.2021.103128. Epub 2021 Jul 9.
PubMed 34280679Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, Reiss AL, Greicius MD. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci. 2007 Feb 28;27(9):2349-56. doi: 10.1523/JNEUROSCI.5587-06.2007.
PubMed 17329432McNicholas N, O'Connell K, Yap SM, Killeen RP, Hutchinson M, McGuigan C. Cognitive dysfunction in early multiple sclerosis: a review. QJM. 2018 Jun 1;111(6):359-364. doi: 10.1093/qjmed/hcx070.
PubMed 28371862Fregni F, Boggio PS, Nitsche M, Bermpohl F, Antal A, Feredoes E, Marcolin MA, Rigonatti SP, Silva MT, Paulus W, Pascual-Leone A. Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory. Exp Brain Res. 2005 Sep;166(1):23-30. doi: 10.1007/s00221-005-2334-6. Epub 2005 Jul 6.
PubMed 15999258
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Anodal tDCS and Virtual Reality on Cognitive Dysfunction in Patients With Multiple Sclerosis: a Protocol of a Double Blind, Randomized, Prospective, Controlled Study.
- ClinicalTrials.gov ID
- NCT07114809
- Acronym / sponsor ID
- tDCScog / 2022/R-Multi/034
- Conditions
- Cognitive Impairment, Multiple Sclerosis
- Keywords
- Cognitive impairment, Multiple Sclerosis, Exergaiming, Virtual Reality, tDCS
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Ospedale Policlinico San MartinoUniversity, hospital or other
- Collaborators
- Italian Multiple Sclerosis Foundation
- Study start
- 2 Sep 2024 (actual)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Jan 2026 (estimated)
- First posted
- 11 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- double blind, randomized, controlled trial
| Arm | Type | Receives |
|---|---|---|
| Experimental group (EG) performing Anodal-tDCS (A-tDCS) and VR | Experimental | Device: Experimental group (EG) performing Anodal-tDCS (A-tDCS) and VREG subjects will undergo a rehabilitative treatment with exergame and concurrent A-tDCS over the left dorsolateral prefrontal cortex. |
| Control group (CG) performing sham-tDCS (S-tCDS) and VR | Sham comparator | Device: Sham Comparator: Control group (CG) performing sham-tDCS (S-tCDS) and VRCG subjects will undergo a rehabilitative treatment with exergame and concurrent S-tDCS over the left dorsolateral prefrontal cortex. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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).
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Experimental group (EG) performing Anodal-tDCS (A-tDCS) and VRPatients 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. | Device | Experimental group (EG) performing Anodal-tDCS (A-tDCS) and VR |
| Sham Comparator: Control group (CG) performing sham-tDCS (S-tCDS) and VRCG 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. | Device | Control group (CG) performing sham-tDCS (S-tCDS) and VR |
Primary outcome
Revised Brief Visuo-Spatial Memory test (BVMT-R)
Time frame: 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)
Symbol digit modalities test (SDMT)
Time frame: 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)
California Verbal Learning test II edition (CVLT-II)
Time frame: 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)
Time frame: 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)
3 secondary outcomes
Multiple Sclerosis Quality of life (MSQoL)
Time frame: The patients will be evaluated at baseline, up to two weeks, one month and six months later
Beck depression inventory scale (BDI)
Time frame: The patients will be evaluated at baseline, up to two weeks, one month and six months later
Fatigue Severity Scale (FSS)
Time frame: The patients will be evaluated at baseline, up to two weeks, one month and six months later
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2025.
- Results publication: PubMed 25927099Laver KE, George S, Thomas S, Deutsch JE, Crotty M. Virtual reality for stroke rehabilitation. Cochrane Database Syst Rev. 2015 Feb 12;2015(2):CD008349. doi: 10.1002/14651858.CD008349.pub3.
- Results publication: PubMed 33129331Cassani R, Novak GS, Falk TH, Oliveira AA. Virtual reality and non-invasive brain stimulation for rehabilitation applications: a systematic review. J Neuroeng Rehabil. 2020 Oct 31;17(1):147. doi: 10.1186/s12984-020-00780-5.
- Results publication: PubMed 10406981Solari A, Filippini G, Mendozzi L, Ghezzi A, Cifani S, Barbieri E, Baldini S, Salmaggi A, Mantia LL, Farinotti M, Caputo D, Mosconi P. Validation of Italian multiple sclerosis quality of life 54 questionnaire. J Neurol Neurosurg Psychiatry. 1999 Aug;67(2):158-62. doi: 10.1136/jnnp.67.2.158.
- Results publication: PubMed 17452283Poreisz C, Boros K, Antal A, Paulus W. Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res Bull. 2007 May 30;72(4-6):208-14. doi: 10.1016/j.brainresbull.2007.01.004. Epub 2007 Jan 24.
- Results publication: PubMed 28225155Charvet L, Shaw M, Dobbs B, Frontario A, Sherman K, Bikson M, Datta A, Krupp L, Zeinapour E, Kasschau M. Remotely Supervised Transcranial Direct Current Stimulation Increases the Benefit of At-Home Cognitive Training in Multiple Sclerosis. Neuromodulation. 2018 Jun;21(4):383-389. doi: 10.1111/ner.12583. Epub 2017 Feb 22.
- Results publication: PubMed 26014600Mattioli F, Bellomi F, Stampatori C, Capra R, Miniussi C. Neuroenhancement through cognitive training and anodal tDCS in multiple sclerosis. Mult Scler. 2016 Feb;22(2):222-30. doi: 10.1177/1352458515587597. Epub 2015 May 26.
- Results publication: PubMed 22357892Filippi M, Riccitelli G, Mattioli F, Capra R, Stampatori C, Pagani E, Valsasina P, Copetti M, Falini A, Comi G, Rocca MA. Multiple sclerosis: effects of cognitive rehabilitation on structural and functional MR imaging measures--an explorative study. Radiology. 2012 Mar;262(3):932-40. doi: 10.1148/radiol.11111299.
- Results publication: PubMed 15006652Mainero C, Caramia F, Pozzilli C, Pisani A, Pestalozza I, Borriello G, Bozzao L, Pantano P. fMRI evidence of brain reorganization during attention and memory tasks in multiple sclerosis. Neuroimage. 2004 Mar;21(3):858-67. doi: 10.1016/j.neuroimage.2003.10.004.
- Results publication: PubMed 10990547Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000 Sep 15;527 Pt 3(Pt 3):633-9. doi: 10.1111/j.1469-7793.2000.t01-1-00633.x.
- Results publication: PubMed 34725881Hiew S, Nguemeni C, Zeller D. Efficacy of transcranial direct current stimulation in people with multiple sclerosis: a review. Eur J Neurol. 2022 Feb;29(2):648-664. doi: 10.1111/ene.15163. Epub 2021 Nov 19.
- Results publication: PubMed 33178103Grigorescu C, Chalah MA, Lefaucheur JP, Kumpfel T, Padberg F, Ayache SS, Palm U. Effects of Transcranial Direct Current Stimulation on Information Processing Speed, Working Memory, Attention, and Social Cognition in Multiple Sclerosis. Front Neurol. 2020 Oct 15;11:545377. doi: 10.3389/fneur.2020.545377. eCollection 2020.
- Results publication: PubMed 34280679Nascimento AS, Fagundes CV, Mendes FADS, Leal JC. Effectiveness of Virtual Reality Rehabilitation in Persons with Multiple Sclerosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Mult Scler Relat Disord. 2021 Sep;54:103128. doi: 10.1016/j.msard.2021.103128. Epub 2021 Jul 9.
- Individual participant dataSharing planned: 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.
Related trials for Cognitive Impairment
Recruiting
Telehealth-Adapted Compensatory Training and Intervention for Cognition
MCI, Mild Cognitive Impairment
Active, not recruitingPhase 2
Effect of Equol Supplementation on Arterial Stiffness and Cognition in Healthy Volunteers
Arterial Stiffness, White Matter Lesions
Recruiting
Neurobehavioral Changes Following Spaceflight Stressors
Stressor, Individual, Alcohol Impairment
RecruitingPhase 1
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
Recruiting
Treating Insomnia in Mild Cognitive Impairment
Mild Cognitive Impairment (MCI), Insomnia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Laura Mori, MD, PhD principal investigator
Ospedale Policlinico San Martino IRCCS
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Experimental group (EG) performing Anodal-tDCS (A-tDCS) and VR in people with Cognitive Impairment and Multiple Sclerosis, run by Ospedale Policlinico San Martino at 3 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Laura Mori, MD, PhD (*39 010 555 5645, laura.mori@hsanmartino.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Revised Brief Visuo-Spatial Memory test (BVMT-R) (time frame: The patients will be evaluated at baseline, up to two weeks, one month and six months later). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07114809, which also lists 21 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2025.