Clinical trial NCT05650281: Silent Progression Activity Monitoring - SPAM Study
Official title: Silent Progression Monitoring in Extreme Phenotypes. SP-MS, Despite an Effective Early Highly Active Treatment as a Paradigm SPAM Study (Silent Progression Activity Monitoring)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Lead sponsor: Centre Hospitalier Universitaire de Nice
Sponsor class: OTHER
First posted: 2022-12-14
Enrollment: 2230
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with RRMS (2017 Mc Donald criteria) treated with highly active treatment in the first 5 years of symptoms onset, at least 1 year, with an EDSS below 4

Brief summary: Real-World Data (RWD) exploring the natural history of MS suggested that relapses do not significantly influence the progression of irreversible disability. Disability progression independent of relapses activity (PIRA) has been confirmed as a frequent relapsing-remitting multiple sclerosis (RRMS) phenomenon based on Randomized Clinical Trials (RCT). Recently, RWD demonstrated that the absence of markers of inflammation (No Evidence of Disease Activity (NEDA) at 2 years did not predict long-term stability. Silent progression has been proposed to describe the insidious disability that accrues many patients who satisfy traditional criteria for relapsing-remitting MS. In this study, the investigators would like to evaluate the occurrence of the SPMS in a population of RRMS patient with an Highly Active Treatment (HAT).


Eligibility criteria: INCLUSION CRITERIA: - Patients with RRMS (2017 Mc Donald criteria) treated with highly active treatment in the first 5 years of symptoms onset, at least 1 year, with an EDSS below 4

* HAT start after April 12th 2007 (availability of Natalizumab)
* Naive or failure (or intolerability) to 1 or more first line DMT (injectables, teriflunomide, DMF).
* EDSS \< or equal 4 when starting HAT EXCLUSION CRITERIA:
* Progressive relapsing MS at baseline
* Clinical or basic MRI data unavailable after on-site visit.
* MS diagnostic \> 5 years at baseline
* Immunosuppressive drugs (Azathioprine, Cyclophosphamide, Mycophenolate, Methotrexate) prescribed before HAT initiation

Primary outcomes:
measure: Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
timeFrame: Baseline: beginning of highly active treatment
measure: Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
timeFrame: Baseline: beginning of highly active treatment
measure: Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
timeFrame: Baseline: beginning of highly active treatment
measure: Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
timeFrame: Baseline: beginning of highly active treatment
measure: Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
timeFrame: Baseline: beginning of highly active treatment
measure: Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
timeFrame: Baseline: beginning of highly active treatment
measure: Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
timeFrame: Baseline: beginning of highly active treatment
measure: Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
timeFrame: Baseline: beginning of highly active treatment
measure: Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
timeFrame: Baseline: beginning of highly active treatment
measure: Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
timeFrame: Baseline: beginning of highly active treatment
measure: Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
timeFrame: Baseline: beginning of highly active treatment
measure: Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
timeFrame: Baseline: beginning of highly active treatment
measure: Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
timeFrame: Baseline: beginning of highly active treatment
measure: Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
timeFrame: Baseline: beginning of highly active treatment
measure: Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
timeFrame: Baseline: beginning of highly active treatment
Secondary outcomes:
measure: To determine re-baseline clinical markers associated with SPMS diagnosis despite an early, practical, HAT.
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: To determine re-baseline clinical markers associated with SPMS diagnosis despite an early, practical, HAT.
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: To determine re-baseline clinical markers associated with SPMS diagnosis despite an early, practical, HAT.
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: To determine re-baseline clinical and MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: Detremination of the impact of different definition of SPMS according to the clinician
timeFrame: Re-baseline definition: any patient with at least an EDSS and MRI examination performed 12 months after HAT onset. +/- 6 months (from 6 to 18 months).
measure: Dertermination of the impact of different definition of SPMS according to Lublin.
timeFrame: at 5 years
measure: Dertermination of the impact of different definition of SPMS according to Lorscheider.
timeFrame: at 5 years
measure: Analyze of the influence of NEDA (No Evidence of Disease activity)
timeFrame: at baseline and at 5 years
measure: Analyze of the influence of MEDA (Mild Evidence of Disease Activity)
timeFrame: at baseline and at 5 years
measure: To find a composite score usable at baseline when prescribing early HAT in clinical practice to predict early SPMS
timeFrame: at 5 years
Other outcomes:
Locations:
city: Nice
country: France
facility: CHU de Nice
Study officials:
References: