Multiple SclerosisEXTREMUSNCT04169750
Home-based EXergames To impRove cognitivE Function in MUltiple Sclerosis
A study testing Exergames and Adaptive COGNI-TRAcK in people with Multiple Sclerosis, run by San Camillo Hospital, Rome at 4 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Exergames and Adaptive COGNI-TRAcK
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 135 participants
- Where
- 4 sitesItaly
- Study dates
- 1 Mar 2020to 30 Sep 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
4 sites in 1 country.
Italy4 sites, 4 recruiting
- Recruiting
Italian MS Foundation
Genova, GE, 16149
Giampaolo Brichetto, +39-10-2713832, giampaolo.brichetto@aism.it
- Recruiting
LaRiCE Lab, Don Gnocchi Foundation IRCCS
Milan, MI, 20148
Davide Cattaneo, +39-2-40308095, dcattaneo@dongnocchi.it
- Recruiting
Dept. of Rehabilitation, M.L. Novarese
Moncrivello, VC, 13040
Claudio Solaro, +39-161-426161, csolaro.centrosm@gmail.com
- Recruiting
A.O. San Camillo, MS Center
Rome, RM, 00152
Luca Prosperini, M, +39-6-58704272, luca.prosperini@gmail.com
About this study
Official title: Home-based EXergames To impRove cognitivE Function in MUltiple Sclerosis: the EXTREMUS Study. A Multicenter, Randomized, Single-blind Non-inferiority Trial
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).
Read more
Investigational interventions:
- 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
- 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
- Sham COGNI-TRAcK: non-adaptive (i.e. constant difficulty level) working memory training delivered by the same app as afore described
Primary endpoint: changes at the Symbol Digit Modalities Test (SDMT), a measure of sustained attention and information processing speed.
Secondary endpoint: changes at the BICAMS (z-scores), a brief, practical and universal assessment tool for cognitive impairment in MS.
Additional endpoints: magnitude of cognitive-motor interference estimated as dual-task cost of balance and walking.
Sample size estimation: The investigators estimated a pre-defined 8-point non-inferiority margin, based on a significant effect of the COGNI-TRAcK in inducing an about 8-point mean increase at SDMT score (with respect to a sham intervention). Accordingly, 35 participants per arm are required to ensure, with an approximately 85%-power level, that the lower limit of a one-side 95% confidence interval will be above the pre-defined non-inferiority margin. Therefore, considering also a drop-out rate of 25%, a total of 132 subjects should be enrolled.
- Conditions
- Multiple Sclerosis
- Being tested
- Exergames, Adaptive COGNI-TRAcK, Sham COGNI-TRAcK
- Keywords
- Rehabilitation, Cognitive impairment, Exergames, Neuroplasticity, Clinical Trial
- Medical subject headings
- Multiple Sclerosis, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExergamesBehavioural
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".
Adaptive COGNI-TRAcKBehavioural
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.
Sham COGNI-TRAcKBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Exergames | Experimental | Not described Receives: Behavioral: Exergames |
| Adaptive COGNI-TRAcK | Active comparator | Not described Receives: Behavioral: Adaptive COGNI-TRAcK |
| Sham COGNI-TRAcK | Sham comparator | Not described Receives: Behavioral: Sham COGNI-TRAcK |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from randomization to 8-week visit
Secondary outcomes (2)
Brief International Cognitive Assessment for Multiple Sclerosis
Brief cognitive assessment for multiple sclerosis that includes the Symbol Digit Modalities Test (SDMT) for exploring sustained attention, the initial learning trials of the second edition of the California Verbal Learning Test (CVLT2) for exploring auditory/verbal learning, and the revised Brief Visuospatial Memory Test (BVMTR) for exploring visual/spatial memory.
Range score: not applicable. Higher scores mean a better outcome.
Measured: At randomization, 8 weeks and 16 weeks
Stroop Color-Word Test
The test explores some aspects of executive functions and consists of naming the color of the ink of words, indicating conflicting colors as quickly as possible.
Range score: not applicable. Higher scores mean a better outcome.
Measured: At randomization, 8 weeks and 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2019
- Study start1 Mar 2020
- Primary completion30 Jun 2022 (estimated)
- Study completion30 Sep 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies 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
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 135 participants (estimated)
Sponsor and investigators
- Lead sponsor
- San Camillo Hospital, Rome
- Sponsor type
- University, hospital or other
- Collaborators
- Fondazione Don Carlo Gnocchi ETS, Fondazione Italiana Sclerosi Multipla, Rehabilitation Unit 'Mons. L. Novarese' Hospital, Moncrivello (VC), IT, University of Chieti
- Responsible party
- Principal investigator, Luca Prosperini, San Camillo Hospital, Rome
- Investigators
- Luca Prosperini, MD, PhD, Principal investigator, A.O. San Camillo-Forlanini
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04169750
- Sponsor's protocol ID
- 2017/R/22
- Acronym
- EXTREMUS
- Status last verified
- Sep 2021
- First submitted
- 3 Nov 2019
- Last updated
- 1 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in a publication
Publications
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. 2026 Feb 13;97(3):217-228. doi: 10.1136/jnnp-2025-336609.
PubMed 41033785
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Home-based EXergames To impRove cognitivE Function in MUltiple Sclerosis: the EXTREMUS Study. A Multicenter, Randomized, Single-blind Non-inferiority Trial
- ClinicalTrials.gov ID
- NCT04169750
- Acronym / sponsor ID
- EXTREMUS / 2017/R/22
- Conditions
- Multiple Sclerosis
- Keywords
- Rehabilitation, Cognitive impairment, Exergames, Neuroplasticity, Clinical Trial
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 135 participants (estimated)
- Lead sponsor
- San Camillo Hospital, RomeUniversity, hospital or other
- Collaborators
- Fondazione Don Carlo Gnocchi ETS, Fondazione Italiana Sclerosi Multipla, Rehabilitation Unit 'Mons. L. Novarese' Hospital, Moncrivello (VC), IT, University of Chieti
- Study start
- 1 Mar 2020 (actual)
- Primary completion
- 30 Jun 2022 (estimated)
- Study completion
- 30 Sep 2022 (estimated)
- First posted
- 20 Nov 2019 (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.
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:
- 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
- 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
- Sham COGNI-TRAcK: non-adaptive (i.e. constant difficulty level) working memory training delivered by the same app as afore described
Primary endpoint: changes at the Symbol Digit Modalities Test (SDMT), a measure of sustained attention and information processing speed.
Secondary endpoint: changes at the BICAMS (z-scores), a brief, practical and universal assessment tool for cognitive impairment in MS.
Additional endpoints: magnitude of cognitive-motor interference estimated as dual-task cost of balance and walking.
Sample size estimation: The investigators estimated a pre-defined 8-point non-inferiority margin, based on a significant effect of the COGNI-TRAcK in inducing an about 8-point mean increase at SDMT score (with respect to a sham intervention). Accordingly, 35 participants per arm are required to ensure, with an approximately 85%-power level, that the lower limit of a one-side 95% confidence interval will be above the pre-defined non-inferiority margin. Therefore, considering also a drop-out rate of 25%, a total of 132 subjects should be enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Exergames | Experimental | Behavioral: Exergames |
| Adaptive COGNI-TRAcK | Active comparator | Behavioral: Adaptive COGNI-TRAcK |
| Sham COGNI-TRAcK | Sham comparator | Behavioral: Sham COGNI-TRAcK |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (8 listed)
- 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;
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 |
|---|---|---|
| ExergamesThe 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". | Behavioural | Exergames |
| Adaptive COGNI-TRAcKThe 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. | Behavioural | Adaptive COGNI-TRAcK |
| Sham COGNI-TRAcKThe 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. | Behavioural | Sham COGNI-TRAcK |
Primary outcome
Symbol Digit Modalities Test
Time frame: Change from randomization to 8-week visit
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.
2 secondary outcomes
Brief International Cognitive Assessment for Multiple Sclerosis
Time frame: At randomization, 8 weeks and 16 weeks
Stroop Color-Word Test
Time frame: At randomization, 8 weeks and 16 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2021.
- Derived from this study: PubMed 41033785Prosperini 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. 2026 Feb 13;97(3):217-228. doi: 10.1136/jnnp-2025-336609.
- Individual participant dataSharing planned: Yes. All IPD that underlie results in a publication
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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. This study is not recruiting at the moment.
Luca Prosperini, MD, PhD principal investigator
A.O. San Camillo-Forlanini
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exergames and Adaptive COGNI-TRAcK in people with Multiple Sclerosis, run by San Camillo Hospital, Rome at 4 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 6 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 1 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Letizia Castelli, MD, PhD (+39658704272, letizia.castelli@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Symbol Digit Modalities Test (time frame: Change from randomization to 8-week visit). 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 NCT04169750, which also lists 1 linked publication.
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 1 Oct 2021.