Clinical trial NCT06303024: Targeting Subclinical Motor and Cognitive Impairment in Patients With Early Onset Multiple Sclerosis
Official title: Targeting Subclinical Motor and Cognitive Impairment in Patients With Early Onset Multiple Sclerosis at High Risk of disEase Acitivity Through a Preventive personaLised and InnovAtive rehaBiLitation stratEgy. (RELIABLE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Multiple Sclerosis, Relapsing-Remitting
Lead sponsor: Fondazione Don Carlo Gnocchi Onlus
Sponsor class: OTHER
Collaborators: name: Careggi Hospital
name: Sheba Medical Center
name: Uppsala University
First posted: 2024-03-12
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: This is a multicentric no-profit pilot study, composed by two phases. I phase: observational prospective study II phase: interventional study
Primary purpose: TREATMENT

Brief summary: Our project proposal is based on an individualized rehabilitation approach in patients with early stage relapsing remission (RR) MS. This approach will be based on risk stratification obtained using several clinical and demographic parameters that are not commonly used in clinical practice. This risk score will be obtained from an extensive neuropsychological, psychosocial and physical assessment to which patients will undergo at baseline and at one-year follow-up.The risk score will allow a better stratification of patients' risk of disease worsening/progression and the application of a preventive and personalized strategy.

Detailed description: This is a multicentric no-profit pilot study, composed by two phases. The objective of the first phase is to create a multi-factorial assessment and prognostic profiling into different risk categories, integrating different techniques in a common evaluation approach. MS patients, referred to the MS Centers of Careggi University Hospital and the Sheba Medical Centre in Tel-Aviv, will be recruit and assess at baseline and 12-months follow-up using a comprehensive approach. The patients will undergo an advanced motor performance evaluation, neuropsychological assessment, and a brain MRI scan to evaluate the presence of new/enlarging T2 lesions, new gadolinium-positive lesions, and volumetric analyses (e.g., total brain volume, grey matter volume, white matter volume, T2 lesions volume, normalized thalamic and hippocampal volume). Data collected from the comprehensive baseline and 12 months assessment will be used to generate a risk score for disease worsening in the short-term, classifying the patients into low/mild, moderate, or high risk. All the variables significantly associated with disease activity will be combined in the risk score.The objectives of II Phase are to apply the previously obtained risk score on a novel cohort using the same inclusion/exclusion criteria; to evaluate the impact of a combined rehabilitation approach in reducing the proportion of patients with disease activity.The risk score obtained from follow-up data of the test cohort applied to the newly recruited patients. Only patients with moderate to high risk of worsening in this new cohort will be included in the rehabilitation program. The included patients will receive an innovative and personalized rehabilitation approach, including counselling on lifestyle habits, an aerobic moderate to high-intensity physical training and a computerized cognitive rehabilitation program.The efficacy of the rehabilitation approach will be then evaluated by comparing patients included in this cohort with patients in the same risk groups included in the phase 1 cohort. Across Phases of the study, Uppsala University partner, will conduct a surveillance and will consider Social and ethical aspects of the integrated rehabilitation approach. Personalized preventive interventions and tailored risk information may raise pressing ethical issues that need careful reflection.

Eligibility criteria: Inclusion Criteria:

* diagnosis of RRMS based on the 2017 McDonald criteria;
* age ≥ 18 years;
* EDSS ≤ 2.0;
* disease duration ≤ 5 years;
* verification of MS subtype,
* duration of disease and EDSS will be accomplished by obtaining a signed consent form for the release of medical information from the treating neurologist.

Exclusion Criteria:

* history of relevant psychiatric comorbidities.
* Severely depressed subjects assessed through the Beck Depression Inventory (scores ≥ 29);
* relapses or corticosteroid treatment in the 30 days before inclusion;
* history of substance abuse;
* presence of non-MS related physical or cognitive impairment that could make the patient unable to complete the study assessments.

Primary outcomes:
measure: Symbol Digit Modalities Test (SDMT)
timeFrame: baseline and 1 year followup cohort 1; baseline, 3 months and 1 year followup cohort 2
measure: California Verbal Learning Test second edition (CVLT-II)
timeFrame: baseline and 1year followup cohort 1; baseline, 3 months and 1year followup cohort 2
measure: Brief Visuo-Spatial Memory Test- Revised (BVMT-R)
timeFrame: baseline and 1 year followup cohort 1; baseline, 3 months and 1year followup cohort 2
measure: Word list generation (WLG)
timeFrame: baseline and 1year followup cohort 1; baseline, 3 months and 1year followup cohort 2
measure: Stroop test
timeFrame: baseline and 1year followup cohort 1; baseline, 3 months and 1year followup cohort 2
measure: Test Intelligenza Breve (TIB)
timeFrame: baseline cohort 1 and baseline cohort 2
measure: 9 hole peg test (9HPT)
timeFrame: baseline and 1year followup cohort 1; baseline, 3 months and 1year followup cohort 2
measure: The Hospital Anxiety and Depression Scale (HADS)
timeFrame: baseline and 1year followup cohort 1; baseline, 3 months and 1 year followup cohort 2
measure: Beck Depression Inventory second edition
timeFrame: baseline and 1year followup cohort 1; baseline, end 3 months and 1year followup cohort 2
measure: The Modified Fatigue Impact Scale (MFIS)
timeFrame: baseline and 1year followup cohort 1; baseline, 3 months and 1year followup cohort 2
measure: The Multiple Sclerosis Walking Scale (MSWS-12)
timeFrame: baseline and 1year followup cohort 1; baseline, 3 months and 1year followup cohort 2
measure: Multiple Sclerosis Impact Scale (MSIS-29-V2)
timeFrame: baseline and 1yearfollowup cohort 1; baseline, 3 months and 1year followup cohort 2
measure: Multiple Sclerosis Quality of Life-54 (MSQOL-54)
timeFrame: baseline and 1year followup cohort 1; baseline, 3 months and 1year followup cohort 2
measure: six minutes walking test (6MWT)
timeFrame: baseline and 1year followup cohort 1; baseline, 3 months and 1year followup cohort 2
measure: Romberg test
timeFrame: baseline and 1year followup cohort 1; baseline, 3 months and 1year followup cohort 2
measure: handgrip test
timeFrame: baseline and 1year followup cohort 1; baseline, 3 months and 1year followup cohort 2
measure: cognitive-motor interference
timeFrame: baseline and 1year followup cohort 1; baseline, 3 months and 1year followup cohort 2
measure: Timed 25-foot walk
timeFrame: baseline and 1year followup cohort 1; baseline, 3 months and 1year followup cohort 2
measure: brain MRI scan
timeFrame: baseline and 1 year followup cohort 1 and 2
measure: International Physical Activity Questionnaire (IPAQ)
timeFrame: baseline and 1 year followup cohort 1 and 2
Secondary outcomes:
Other outcomes:
Locations:
city: Firenze
country: Italy
facility: IRCCS Fondazione Don Carlo Gnocchi ONLUS
Study officials:
References: