Clinical trial NCT04169750: Home-based EXergames To impRove cognitivE Function in MUltiple Sclerosis
Official title: Home-based EXergames To impRove cognitivE Function in MUltiple Sclerosis: the EXTREMUS Study. A Multicenter, Randomized, Single-blind Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Multiple Sclerosis
Keywords: Rehabilitation
Cognitive impairment
Exergames
Neuroplasticity
Clinical Trial
Lead sponsor: San Camillo Hospital, Rome
Sponsor class: OTHER
Collaborators: name: Fondazione Don Carlo Gnocchi Onlus
name: Fondazione Italiana Sclerosi Multipla
name: Rehabilitation Unit 'Mons. L. Novarese' Hospital, Moncrivello (VC), IT
name: University of Chieti
First posted: 2019-11-20
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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. 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. 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. 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Symbol Digit Modalities Test
timeFrame: Change from randomization to 8-week visit
Secondary outcomes:
measure: Brief International Cognitive Assessment for Multiple Sclerosis
timeFrame: At randomization, 8 weeks and 16 weeks
measure: Stroop Color-Word Test
timeFrame: At randomization, 8 weeks and 16 weeks
Other outcomes:
measure: Cognitive-Motor Interference
timeFrame: At randomization, 8 weeks and 16 weeks
measure: 29-item Multiple Sclerosis Impact Scale
timeFrame: At randomization, 8 weeks and 16 weeks
measure: 21-item Modified Fatigue Impact Scale
timeFrame: At randomization, 8 weeks and 16 weeks
measure: Work Productivity and Activity Impairment: Multiple Sclerosis
timeFrame: At randomization, 8 weeks and 16 weeks
measure: Time to first accidental falls
timeFrame: From randomization to study termination (16 weeks)
measure: Adverse events
timeFrame: From randomization to study termination (16 weeks)
Locations:
city: Genova
country: Italy
facility: Italian MS Foundation
state: GE
city: Milano
country: Italy
facility: LaRiCE Lab, Don Gnocchi Foundation IRCCS
state: MI
city: Rome
country: Italy
facility: A.O. San Camillo, MS Center
state: RM
city: Moncrivello
country: Italy
facility: Dept. of Rehabilitation, M.L. Novarese
state: VC
Study officials:
affiliation: A.O. San Camillo-Forlanini
name: Luca Prosperini, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: