msNEUROPLAST: Neuroplasticity of Cortical Areas Induced by Cognitive Training in Patients With Multiple Sclerosis MS-NEUROPLAST

Sponsor

Aristotle University Of Thessaloniki (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04806568

Collaborator

King Fahad Medical City (Other)

Enrollment

Location

Arms

35.9

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This clinical study aims to identify MS related beneficial plasticity and by contrast maladaptive reorganization in combination with elements of daily functional status as a response to a cognitive training program

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis Cognitive Decline	Other: Cognitive Training	N/A

Detailed Description

"Cognitive decline is a debilitating and widespread comorbidity of Multiple Sclerosis (MS) affecting up to 65 percent of patients with MS (PwMS). Cognitive changes can be the only behavioral index of MS activity. But how accurately and timely can these be captured? The existing clinical tools are subjective and do not have the dynamic of prognosis. It remains uncertain how much change in cognitive status is required to translate into a meaningful clinical outcome and how long it may subsequently take to become apparent. Moving towards a holistic approach, MS-NEUROPLAST aims to further expand previously-published prognostic marker candidates and previous work of the applicant and the members of the research team and employ a group of methodologies for interventions and applications which will quantify via real-world assessment the MS-related cognitive changes in order to characterize not only decline but given the right dosage of stimulation improvement as well.

MS-NEUROPLAST has three main objectives:

(i) Utilize state of-the-art neuroimaging and network science measures to more thoroughly understand neural indices of cognitive impairment in PwMS.

(ii) Evaluate the efficacy for treating MS-associated cognitive deficits using a computerized cognitive training treatment by determining the differences, between subjects treated with cognitive training and controls, on network science measures indexing network efficiency or collapse and on the performance of a battery of neuropsychological tests that are frequently impaired in MS.

(iii) Investigate the dissociation of the cortical mechanisms related to training-induced plasticity and maladaptive reorganization (namely separate good from bad), by taking into account the homeostatic capacity of the human organism as a whole and thus examining whether the correlation of the neurophysiological and cognitive indices with longitudinal digital biomarkers of daily functional status can capture the underlying pathology.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants are assigned to either the intervention or control group.Participants are assigned to either the intervention or control group.

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Cognitive Decline Prognosis in Multiple Sclerosis: Effectiveness of a Computerized Cognitive Training Treatment on Cortical Reorganization

Actual Study Start Date :

Dec 1, 2020

Anticipated Primary Completion Date :

Nov 30, 2023

Anticipated Study Completion Date :

Nov 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PwMS-CogTr Adult individuals with Multiple Sclerosis that will follow a cognitive training intervention.	Other: Cognitive Training The cognitive training treatment is a Greek adaptation of BrainHQ developed by Posit Science Corporation. The intervention will target speed, attention, working memory, and executive function through the visual and auditory domains via a set of 15 exercises. Each daily training session consists of four exercises chosen from an active set of six. Participants will be instructed to train for one hour per day, three days per week, over 12 weeks via a tablet or a laptop. Each subject will receive at least 20 sessions of computerized cognitive training.
No Intervention: PwMS-Con Adult individuals with Multiple Sclerosis serving as passive controls.

Arm

Intervention/Treatment

Experimental: PwMS-CogTr

Adult individuals with Multiple Sclerosis that will follow a cognitive training intervention.

Other: Cognitive Training

The cognitive training treatment is a Greek adaptation of BrainHQ developed by Posit Science Corporation. The intervention will target speed, attention, working memory, and executive function through the visual and auditory domains via a set of 15 exercises. Each daily training session consists of four exercises chosen from an active set of six. Participants will be instructed to train for one hour per day, three days per week, over 12 weeks via a tablet or a laptop. Each subject will receive at least 20 sessions of computerized cognitive training.

No Intervention: PwMS-Con

Adult individuals with Multiple Sclerosis serving as passive controls.

Outcome Measures

Primary Outcome Measures

Change in current density strength of the cortical activity as measured via EEG [1 month]
Changes in cortical activity strength caused via the training. Change is defined as statistical significance in the t-test comparison of the current density strength as reconstructed via Low Resolution Electromagnetic Tomography (LORETA) algorithm on the basis of high-density EEG recordings, before compared to after the training.
Change in cortical connectivity as measured via EEG [1 month]
Changes in cortical connectivity caused via the training. Change is defined as statistical significance in the t-test comparison of Phase Transfer Entropy estimated from the cortical activity, as reconstructed via LORETA algorithm on the basis of high density EEG recordings, before compared to after the training.

Secondary Outcome Measures

Change in cognitive capacity [1 month]
Change of scoring in neuropsychological tests related to memory, attention, and executive function. Change is defined as statistical significance in the comparison between before and after the training. The Brief International Cognitive Assessment for MS (BICAMS) will be used to perform cognitive evaluation. It consists of: the Symbol Digit Modalities Test (SDMT) for processing speed assessment. The score of the test is the number of correct answers in 90 seconds. (higher is better) the California Verbal Learning Test (CVLT2) for auditory/verbal learning assessment. The score output is between 0 and 80 (higher is better). the revised Brief Visuospatial Memory Test (BVMTR) for visual/spatial memory assessment. The score output is between 0 and 12 (higher is better).
Change in neurologic impairment [1 month]
Change of scoring in neurologic impairment test. Change is defined as statistical significance in the comparison between before and after the training. The test that will be used is the EDSS. It consists of scores in each of seven functional systems (FSs) and an ambulation score that are then combined to determine the EDSS steps, ranging from 0 (normal) to 10 (death). The FSs are Visual, Brainstem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, and Cerebral functions.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male/female patients aged 18 to 55 years at screening
Diagnosis of MS according to the 2017 Revised McDonald criteria
Disability status at screening with an EDSS score of 0 to 5.5
Relapsing MS and progressive MS as defined by Lublin
Disability status at screening with an EDSS score of 0 to 5.5
Neurologically stable within 1 month prior to screening
Years from MS diagnosis: ≤ 10 for relapsing patients, ≤ 15 for progressive patients
Patients receiving the same Disease Modifying Treatment (DMT) for at least 6 months

Exclusion Criteria:

Patients suspected of not being able or willing to cooperate or comply with study protocol requirements
Patients meeting criteria for other demyelinating diseases of the CNS
Patients with active chronic disease (or stable but treated with immune therapy) of the immune system other than MS
Patients with any other significant CNS disease or serious psychiatric disorder which can interfere with the patient's ability to cooperate or comply with the study procedure
Patients unable or unwilling to undergo MRI scans and EEG