NCT04169750

Brief Summary

Study design: Phase II, multicenter, randomized, sham-controlled, single-blind, parallel arm, multicenter study to test the hypothesis that home-based exergames is not inferior to home-based cognitive rehabilitation delivered by a software application (app) for mobile devices and both interventions are superior to a placebo-analogue cognitive intervention in improving cognitive function and reducing cognitive-motor interference in people with multiple sclerosis (MS). Procedures: Participants will be randomized in a 1:1:1 ratio to receive an 8-week home-based training with exergames (intervention of interest) or adaptive COGNI-TRAcK (comparator intervention) or sham COGNI-TRAcK (placebo-analogue intervention). Study assessment will be done at study enrolment (baseline), at the end of the 8-week intervention period (immediate post-training, Week 8) and after 16 weeks from randomization (post-training follow-up, Week 16). Investigational interventions:

  1. 1.Exergames: home-based repetition of several games delivered by the Nintendo © Wii Balance Board, a commercial off-the-shelf video game console for re-training of balance and postural strategies
  2. 2.Adaptive COGNI-TRAcK: adaptive (i.e. automatic adjustment of tasks difficulty) working memory training delivered by a customized application software for mobile devices to self-administer at-home
  3. 3.Sham COGNI-TRAcK: non-adaptive (i.e. constant difficulty level) working memory training delivered by the same app as afore described

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
135

participants targeted

Target at P75+ for not_applicable multiple-sclerosis

Timeline
Completed

Started Mar 2020

Typical duration for not_applicable multiple-sclerosis

Geographic Reach
1 country

4 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 3, 2019

Completed
17 days until next milestone

First Posted

Study publicly available on registry

November 20, 2019

Completed
3 months until next milestone

Study Start

First participant enrolled

March 1, 2020

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2022

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2022

Completed
Last Updated

October 1, 2021

Status Verified

September 1, 2021

Enrollment Period

2.3 years

First QC Date

November 3, 2019

Last Update Submit

September 30, 2021

Conditions

Multiple Sclerosis

Keywords

RehabilitationCognitive impairmentExergamesNeuroplasticityClinical Trial

Outcome Measures

Primary Outcomes (1)

  • Symbol Digit Modalities Test

    The participant is presented with a page headed by a key that pairs the single digits 1-9 with nine symbols. Rows below contain only symbols, the subject's task is to orally report the correct number in the spaces below. After completing the first 10 items with guidance, the subject is timed to determine how many responses can be made in 90 seconds. Range score: not applicable. Higher scores mean a better outcome. Explored domain: Sustained attention and information processing speed.

    Change from randomization to 8-week visit

Secondary Outcomes (2)

  • Brief International Cognitive Assessment for Multiple Sclerosis

    At randomization, 8 weeks and 16 weeks

  • Stroop Color-Word Test

    At randomization, 8 weeks and 16 weeks

Other Outcomes (6)

  • Cognitive-Motor Interference

    At randomization, 8 weeks and 16 weeks

  • 29-item Multiple Sclerosis Impact Scale

    At randomization, 8 weeks and 16 weeks

  • 21-item Modified Fatigue Impact Scale

    At randomization, 8 weeks and 16 weeks

  • +3 more other outcomes

Study Arms (3)

Exergames

EXPERIMENTAL
Behavioral: Exergames

Adaptive COGNI-TRAcK

ACTIVE COMPARATOR
Behavioral: Adaptive COGNI-TRAcK

Sham COGNI-TRAcK

SHAM COMPARATOR
Behavioral: Sham COGNI-TRAcK

Interventions

ExergamesBEHAVIORAL

The training protocol will be delivered by the Nintendo ® Wii balance board and consists of repetitions of several games selected from the "Wii Fit Plus" package (http:// www.wiifit.com/training/balance-games.html). Each game starts at basic level, and when a certain score is reached, patients is automatically transferred to a more advanced level. Patients will be encouraged to play the next game if they have a level progress; otherwise, 10 minutes will be allocated for each game. During the first 4 weeks of training, patients will be allowed to play only "Zazen" (sitting position), "Table Tilt" and "Ski Slalom"; thereafter they will add the remaining games "Penguin Slide", "Tightrope Walk", "Balance Bubble" and "Soccer Heading".

Exergames
Adaptive COGNI-TRAcKBEHAVIORAL

The training protocol will be delivered by a dedicated app for mobile devices (mobile phone or tablet). The app implements three different types of exercises (each one executed for about 10 min a session), consisting in a visuo-spatial working memory task, an "operation" N-back task and a "dual" N-back task. The adaptive training is structured so that the exercises difficulty level will increase by one step every time the user will perform a correct exercise. On the other hand, the difficulty level will decrease by one step if the exercise is incorrect for three times in a row.

Adaptive COGNI-TRAcK
Sham COGNI-TRAcKBEHAVIORAL

The training protocol will be delivered by a dedicated app for mobile devices (mobile phone or tablet) as previously described for adaptive COGNI-TRAcK. However, the non-adaptive training (placebo-analogue intervention) consists in an algorithm implementing two low difficulty levels alternating every day regardless of the user's performance.

Sham COGNI-TRAcK

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • age between 18 and 55 years (inclusive);
  • cognitive impairment, defined as failure in the SDMT, defined as a corrected score less than 38, i.e. below the 5th percentile of normative value;
  • Expanded Disability Status Scale (EDSS) score between 2.0 and 5.5;
  • ability to stand upright for at least 180 seconds without any support;
  • ability to understand and comply with study requirements;
  • ability to provide a valid informed consent before any study procedure.

You may not qualify if:

  • relapse in the previous 6 months;
  • initiation of disease-modifying or symptomatic treatments or physiotherapy programme in the 3 months prior to study entry;
  • any medication/physiotherapy changes occurring over the previous 3 months;
  • significant visual impairment, defined as a Visual System scoring more than 2 at the Kurtzke Functional Systems Score;
  • clinically relevant depression, defined as Beck Depression Inventory-II (BDI-II) score equal or more than 14;
  • overt dementia, defined as an adjusted Mini Mental State Examination (MMSE) score equal or less than 24;
  • history of epilepsy or seizures;
  • any medical condition, including musculoskeletal disorders that can interfere with the study conduction.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Italian MS Foundation

Genova, GE, 16149, Italy

RECRUITING

LaRiCE Lab, Don Gnocchi Foundation IRCCS

Milan, MI, 20148, Italy

RECRUITING

A.O. San Camillo, MS Center

Rome, RM, 00152, Italy

RECRUITING

Dept. of Rehabilitation, M.L. Novarese

Moncrivello, VC, 13040, Italy

RECRUITING

Related Publications (1)

  • Prosperini L, Tacchino A, Ruggieri S, Brichetto G, Podda J, Anastasi D, Cardini R, Corrini C, Quartuccio ME, Alcamisi I, Di Giovanni R, Gamberini G, Grange E, Pietrolongo E, Rispoli MG, Tomassini V, Cattaneo D, Solaro C. Home-based EXergames To impRovE cognitive function in MUltiple Sclerosis (EXTREMUS). J Neurol Neurosurg Psychiatry. 2025 Oct 1:jnnp-2025-336609. doi: 10.1136/jnnp-2025-336609. Online ahead of print.

    PMID: 41033785DERIVED

MeSH Terms

Conditions

Multiple SclerosisCognitive Dysfunction

Interventions

Exergaming

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System DiseasesCognition DisordersNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

ExerciseMotor ActivityMovementMusculoskeletal Physiological PhenomenaMusculoskeletal and Neural Physiological Phenomena

Study Officials

  • Luca Prosperini, MD, PhD

    A.O. San Camillo-Forlanini

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Letizia Castelli, MD, PhD

CONTACT

+39658704272letizia.castelli@gmail.com

Shalom Haggiag, MD

CONTACT

+39658704272lvshalom@hotmail.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

November 3, 2019

First Posted

November 20, 2019

Study Start

March 1, 2020

Primary Completion

June 30, 2022

Study Completion

September 30, 2022

Last Updated

October 1, 2021

Record last verified: 2021-09

Data Sharing

IPD Sharing
Will share

All IPD that underlie results in a publication

Shared Documents
STUDY PROTOCOL, ICF
Time Frame
After publication
Access Criteria
Upon request to PI

Locations

IT(4)