Function Magnetic Resonance Imaging to Assess Two Therapeutic Strategies in Multiple Sclerosis (NeuroRehEM). (NeuroRehEM)

Neurorehabilitation and Functional Recovery in Multiple Sclerosis: Assessing Two Therapeutic Strategies Using Functional Magnetic Resonance Imaging.

Multiple sclerosis (MS) is an autoimmune disease that causes cognitive and motor disabilities and contributes to decrease patients life quality. Previous results described that there are some MS patients that showed (at least in some phases of the disease) neuroplasticity processes that are able to compensate some cognitive deficits. Moreover, neuroplasticity processes seem to be limited and related to the degree of gray matter atrophy (patients with less atrophy show grater neuroplasticity than those with higher atrophy level). The aims of this project are:

1. to study behavioral changes (post-training) induced by two different rehabilitation programs: a)cognitive training focused on exclusively enhancing working memory and b) aerobic + cognitive training aimed to enhance attention, working memory processes and motor capabilities using a virtual reality game.
2. to study neuroplasticity changes (post-training functional connectivity changes) induced by these rehabilitation programs
3. to observe the role of the atrophy in brain neuroplasticity processes.

Neuropathological status and neuroplasticity processes (studied using neuroimaging tools) as well as cognitive performance using neuropsychological tools will be assessed in a group of MS patients (with different phenotypes) at two different time points: before any training (S1) and after 10 days of training (S2). This project will be financed by the Ministerio de ciencia, innovación y universidades of the Spanish government and also have been approved by the Ethical committee of Universitat Jaume I.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Behavioral: N-back Cognitive Training; Behavioral: Virtual Reality Motor and Cognitive Training

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cristina Forn; Phone Number: +34 964 38 7658; Email: forn@uji.psb.es

Study Locations

• Spain
  • Castellón
    • Castellón De La Plana, Castellón, Spain, 12006
      • Recruiting
      • Universitat Jaume I (ImagoBrain Research Group)
      • Contact: Cristina Forn; Phone Number: +34 964 387658; Email: forn@uji.psb.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Multiple Sclerosis Diagnosis.

Exclusion Criteria:

• Other neurological pathologies comorbidity.
• Magnetic resonance imaging incompatibilities.
• Motor impairment degree that impede the task performance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Working Memory Training in MS patients; This group of patients will perform a computerized n-back training, which includes a sequence of 2-back and 3-back blocks.	Behavioral: N-back Cognitive Training; N-back task mainly trains working memory and information processing speed. This training lasts 10 days (1 hour per day).
Experimental: Virtual Reality Training in MS patients; This group of patients will perform a Virtual Reality "Ball Task" training. This task contains 6 trials of increasing difficulty.	Behavioral: Virtual Reality Motor and Cognitive Training; Virtual Reality "Ball Task" mainly trains inhibitory control, attention, working memory and motor functions. This training lasts 10 days (30 minutes per day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Correct Responses	Number of correct responses in both tasks (n-back computerized task and balls Virtual Reality task)	Baseline and 10 training days after.
Change from baseline in Reaction Time	This is a primary outcome of the n-back task, which refers to the amount of time (in milliseconds) that elapse from the moment the correct stimulus appears and the correct response is given.	Baseline and 10 training days after.
Change from baseline in Omissions	In both tasks will be assessed the number of times that a correct stimulus appear and non-response is given.	Baseline and 10 training days after.
Change from baseline in Errors	The number of times that a distractor stimulus appears and a response is given.	Baseline and 10 training days after.
Change from baseline in Functional Connectivity in resting state	This is a brain activity measure during resting state through functional magnetic resonance imaging. This outcome will be assessed in both studies. fMRI sequence: T2-weighted echoplanar imaging sequence.	Baseline and 10 training days after.
Change from baseline in Functional Connectivity in task performance	This is a brain activity measure during a task performance through functional magnetic resonance imaging. This outcome will be assessed in Virtual Reality study. fMRI sequence: T2-weighted echoplanar imaging sequence.	Baseline and 10 training days after.
Change from baseline in SRT-S: Selective Reminding Test (Storing)	A subtest of the BRB-N (The Brief Repeatable Battery of Neuropsychological Tests for MS) which measures memory storage capacity.	Baseline and 10 training days after.
Change from baseline in SRT-R: Selective Reminding Test (Retrieval)	This subtest of the BRB-N is a measure of memory retrieval capacity.	Baseline and 10 training days after.
Change from baseline in SRT-D: Selective Reminding Test (Delayed)	This BRB-N subtest measures the delayed memory.	Baseline and 10 training days after.
Change from baseline in SPART: Spatial Recall Test	A subtest of the BRB-N that measures spatial memory.	Baseline and 10 training days after.
Change from baseline in SPART-D: Spatial Recall Test (Delayed)	This BRB-N subtest measures the spatial delayed memory.	Baseline and 10 training days after.
Change from baseline in SDMT: Symbol Digit Modalities Test	A BRB-N subtest which measures information processing speed.	Baseline and 10 training days after.
Change from baseline in PASAT: Paced Auditory Serial Addition Task	A BRB-N subtest which measures working memory.	Baseline and 10 training days after.
Change from baseline in Phonemic Fluency	A language measure that assesses phonemic fluency.	Baseline and 10 training days after.
Change from baseline in Semantic Fluency	A language measure that assesses semantic fluency.	Baseline and 10 training days after.
Change from baseline in Digit Span Forward	A subtest of the Wechsler Adult Intelligence Scale (WAIS-III) that is an attention measure.	Baseline and 10 training days after.
Change from baseline in Digit Span Backward	A WAIS-III subtest that is a working memory measure.	Baseline and 10 training days after.
Change from baseline in Letters and Numbers	A WAIS-III subtest that measures working memory.	Baseline and 10 training days after.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Intracraneal Volume (TIV)	A measure of brain volumetry. MRI sequence: structural T1-weighted MPRAGE sequence.	Baseline
Brain Parenchimal Fraction (BPF)	MRI sequence: structural T1-weighted MPRAGE sequence.	Baseline
Lesion Volume in white matter tissue	A brain damage volumetry measure. MRI sequence: structural T1-weighted MPRAGE sequence and T2-FLAIR sequence	Baseline
Cortical Lesions	Number of brain cortical lesions. MRI Sequence: inversion recovery MRI pulse sequence (DIR).	Baseline
Cortical Thickness	Brain cortical thickness measure. MRI sequence: structural T1-weighted MPRAGE sequence.	Baseline

Collaborators and Investigators

• Sponsor: Universitat Jaume I
• Investigators: Study Director: Cristina Forn, Universitat Jaume I (Castellón, Spain); Study Director: Carla Sanchis, Universitat Jaume I (Castellón, Spain)

Publications and helpful links

General Publications

• Baltruschat SA, Ventura-Campos N, Cruz-Gomez AJ, Belenguer A, Forn C. Gray matter atrophy is associated with functional connectivity reorganization during the Paced Auditory Serial Addition Test (PASAT) execution in Multiple Sclerosis (MS). J Neuroradiol. 2015 Jun;42(3):141-9. doi: 10.1016/j.neurad.2015.02.006. Epub 2015 Apr 6.
• Cruz-Gomez AJ, Ventura-Campos N, Belenguer A, Avila C, Forn C. The link between resting-state functional connectivity and cognition in MS patients. Mult Scler. 2014 Mar;20(3):338-48. doi: 10.1177/1352458513495584. Epub 2013 Jul 4.
• Mitolo M, Venneri A, Wilkinson ID, Sharrack B. Cognitive rehabilitation in multiple sclerosis: A systematic review. J Neurol Sci. 2015 Jul 15;354(1-2):1-9. doi: 10.1016/j.jns.2015.05.004. Epub 2015 May 9.
• Aguirre N, Cruz-Gomez AJ, Esbri SF, Miro-Padilla A, Bueicheku E, Broseta-Torres R, Avila C, Sanchis-Segura C, Forn C. Enhanced frontoparietal connectivity in multiple sclerosis patients and healthy controls in response to an intensive computerized training focused on working memory. Mult Scler Relat Disord. 2021 Jul;52:102976. doi: 10.1016/j.msard.2021.102976. Epub 2021 Apr 24.
• Sandroff BM, Wylie GR, Sutton BP, Johnson CL, DeLuca J, Motl RW. Treadmill walking exercise training and brain function in multiple sclerosis: Preliminary evidence setting the stage for a network-based approach to rehabilitation. Mult Scler J Exp Transl Clin. 2018 Feb 21;4(1):2055217318760641. doi: 10.1177/2055217318760641. eCollection 2018 Jan-Mar.
• Aguirre N, Cruz-Gomez AJ, Miro-Padilla A, Bueicheku E, Broseta Torres R, Avila C, Sanchis-Segura C, Forn C. Repeated Working Memory Training Improves Task Performance and Neural Efficiency in Multiple Sclerosis Patients and Healthy Controls. Mult Scler Int. 2019 Apr 16;2019:2657902. doi: 10.1155/2019/2657902. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2022
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: January 31, 2022
• First Submitted That Met QC Criteria: March 7, 2022
• First Posted (Actual): March 8, 2022

Study Record Updates

• Last Update Posted (Actual): November 16, 2022
• Last Update Submitted That Met QC Criteria: November 15, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Neuroplasticity; Cognitive Impairment; Magnetic Resonance Imaging; Virtual Reality
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: PID2019-106793RB-I00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Not foreseen due to the ethics committee's privacy policy on the protection of personal data. However, upon request, radiological data could be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No