- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05650281
Silent Progression Activity Monitoring - SPAM Study (SPAM)
July 20, 2023 updated by: Centre Hospitalier Universitaire de Nice
Silent Progression Monitoring in Extreme Phenotypes. SP-MS, Despite an Effective Early Highly Active Treatment as a Paradigm SPAM Study (Silent Progression Activity Monitoring)
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).
Study Overview
Study Type
Observational
Enrollment (Actual)
2230
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Nice, France
- CHU de Nice
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
No
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
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Retrospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Patients
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
|
NO INTERVENTION
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
Time Frame: Baseline: beginning of highly active treatment
|
Age in years
|
Baseline: beginning of highly active treatment
|
Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
Time Frame: Baseline: beginning of highly active treatment
|
Disease duration (which should be <5 years) in months
|
Baseline: beginning of highly active treatment
|
Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
Time Frame: Baseline: beginning of highly active treatment
|
Expanded Disability Status Scale (EDSS) (which must be <4)
|
Baseline: beginning of highly active treatment
|
Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
Time Frame: Baseline: beginning of highly active treatment
|
new T2 lesion(s) on brain MRI and spinal cord MRI (if available)
|
Baseline: beginning of highly active treatment
|
Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
Time Frame: Baseline: beginning of highly active treatment
|
gadolinium enhancement on brain MRI and spinal cord MRI (if available)
|
Baseline: beginning of highly active treatment
|
Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
Time Frame: Baseline: beginning of highly active treatment
|
Interval time between the first and the second relapse in months
|
Baseline: beginning of highly active treatment
|
Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
Time Frame: Baseline: beginning of highly active treatment
|
Reason for HAT: naive, or switch
|
Baseline: beginning of highly active treatment
|
Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
Time Frame: Baseline: beginning of highly active treatment
|
Number of relapses since MS onset
|
Baseline: beginning of highly active treatment
|
Determination of baseline clinical markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
Time Frame: Baseline: beginning of highly active treatment
|
DMT administered since MS onset: number of DMT and type
|
Baseline: beginning of highly active treatment
|
Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
Time Frame: Baseline: beginning of highly active treatment
|
More than 9 T2 lesions on MRI
|
Baseline: beginning of highly active treatment
|
Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
Time Frame: Baseline: beginning of highly active treatment
|
At least 1 periventicular T2 lesion on MRI
|
Baseline: beginning of highly active treatment
|
Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
Time Frame: Baseline: beginning of highly active treatment
|
At least 3 periventicular T2 lesions on MRI
|
Baseline: beginning of highly active treatment
|
Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
Time Frame: Baseline: beginning of highly active treatment
|
At least 1 infratentorial T2 lesion on MRI
|
Baseline: beginning of highly active treatment
|
Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
Time Frame: Baseline: beginning of highly active treatment
|
At least 1 spinal cord T2 lesion on MRI
|
Baseline: beginning of highly active treatment
|
Determination of baseline MRI markers associated with SPMS diagnosis despite an early, practical, Highly Active Treatment.
Time Frame: Baseline: beginning of highly active treatment
|
At least 1 gadolinium enhancement T1 lesion on MRI
|
Baseline: beginning of highly active treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To determine re-baseline clinical markers associated with SPMS diagnosis despite an early, practical, HAT.
Time Frame: 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).
|
Age in years
|
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).
|
To determine re-baseline clinical markers associated with SPMS diagnosis despite an early, practical, HAT.
Time Frame: 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).
|
Disease duration (which should be <5 years) in months
|
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).
|
To determine re-baseline clinical markers associated with SPMS diagnosis despite an early, practical, HAT.
Time Frame: 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).
|
EDSS (which must be <4) +/- 3 months
|
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).
|
To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
Time Frame: 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).
|
new T2 lesion(s) on brain MRI and spinal cord MRI (if available)
|
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).
|
To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
Time Frame: 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).
|
gadolinium enhancement on brain MRI and spinal cord MRI (if available)
|
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).
|
To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
Time Frame: 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).
|
Interval time between the first and the second relapse in months
|
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).
|
To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
Time Frame: 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).
|
Number of relapses since MS onset
|
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).
|
To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
Time Frame: 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).
|
Number of relapse before baseline
|
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).
|
To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
Time Frame: 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).
|
Disease Modifying Therapies (DMT) administered since MS onset
|
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).
|
To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
Time Frame: 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).
|
More than 9 T2 lesions on MRI
|
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).
|
To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
Time Frame: 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).
|
At least 1 periventicular T2 lesion on MRI
|
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).
|
To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
Time Frame: 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).
|
At least 3 periventicular T2 lesion on MRI
|
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).
|
To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
Time Frame: 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).
|
At least 1 infratentorial T2 lesion on MRI
|
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).
|
To determine re-baseline MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
Time Frame: 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).
|
At least 1 spinal cord T2 lesion on MRI
|
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).
|
To determine re-baseline clinical and MRI markers associated with SPMS diagnosis despite an early, practical, HAT.
Time Frame: 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).
|
At least 1 gadolinium enhancement T1 lesion on MRI
|
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).
|
Detremination of the impact of different definition of SPMS according to the clinician
Time Frame: 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).
|
The definition of SPMS according to the clinician : neurological episode = start of progression as assessed by the time to develop SPMS in years.
|
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).
|
Dertermination of the impact of different definition of SPMS according to Lublin.
Time Frame: at 5 years
|
The definition of SPMS according to Lublin : progressive accumulation of disability after a primary relapsing course which must be confirmed at least 6 months after, as assessed by the time to develop SPMS in years.
|
at 5 years
|
Dertermination of the impact of different definition of SPMS according to Lorscheider.
Time Frame: at 5 years
|
The definition of SPMS according to Lorscheider: with a minimum EDSS of 4 , an increase by 1 point if the EDSS was between 4 and 5.5, or an increase by 0.5 points if the EDSS was above 5.5, confirmed after 3 months., as assessed by the time to develop SPMS in years.
|
at 5 years
|
Analyze of the influence of NEDA (No Evidence of Disease activity)
Time Frame: at baseline and at 5 years
|
The disease activity will be evalued by the NEDA score
|
at baseline and at 5 years
|
Analyze of the influence of MEDA (Mild Evidence of Disease Activity)
Time Frame: at baseline and at 5 years
|
The disease activity will be evalued by the MEDA score
|
at baseline and at 5 years
|
To find a composite score usable at baseline when prescribing early HAT in clinical practice to predict early SPMS
Time Frame: at 5 years
|
All baseline variables will be evaluated in association with the prescriptio of an early HAT to predict early SPMS.
|
at 5 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 1, 2023
Primary Completion (Actual)
March 31, 2023
Study Completion (Actual)
March 31, 2023
Study Registration Dates
First Submitted
August 8, 2022
First Submitted That Met QC Criteria
December 5, 2022
First Posted (Actual)
December 14, 2022
Study Record Updates
Last Update Posted (Actual)
July 21, 2023
Last Update Submitted That Met QC Criteria
July 20, 2023
Last Verified
July 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 22Neuro03
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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