BENEFIT 15 Long-term Follow-up Study of the BENEFIT and BENEFIT Follow-up Studies

Study Overview
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Brief Summary
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The purpose of this study is to obtain long-term clinical data from patients approximately 15 years after their first clinical event, who participated in the former BENEFIT 304747 study and were treated at least once within that study. This study will collect clinical information on the disease course, on disability, relapses, cognitive function over time, quality of life, depression, fatigue, resource use, and employment status. In addition, brain MRI is performed.

Official Title
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BENEFIT 15 Long-term Follow-up Study of the BENEFIT and BENEFIT Follow-up Studies

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Other: Brain MRI
* Other: Blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects who were treated at least once in BENEFIT study 304747 are eligible for inclusion in the BENEFIT 15 study Exclusion Criteria: Subjects who, according to the investigator's judgment, have medical, psychiatric, or other conditions that compromise the subject's ability to understand the purpose of the study Suspected clinical instability or unpredictability of the clinical course during the study(e.g., due to previous surgery or acute stroke)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Experimental arm 15 years ago<br>This long term study does not imply current study medication. It looks at the status 15 years after the clinicial trial (BENEFIT) | Other: Brain MRI<br>* Brain MRI will be performed<br>Other: Blood sampling<br>* Blood samples will be taken<br>|
| Other: Placebo arm, offered treatment at MS diagnosis or at Month 24<br>This long term study does not imply current study medication. It looks at the status 15 years after the clinicial trial (BENEFIT) | Other: Brain MRI<br>* Brain MRI will be performed<br>Other: Blood sampling<br>* Blood samples will be taken<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with diagnosis of multiple sclerosis within fifteen years after Clinically-Isolated Syndrome (CIS) according to McDonald 2001 and 2010 criteria |  | Over 15 years since the subject´s first clinical event | 
| Disease course since start of BENEFIT as assessed at the time of BENEFIT 15 |  | Over 15 years since the subject's first clinical event | 
| Time to first relapse |  | Over 15 years since the subject´s first clinical event | 
| Time to recurrent relapse |  | Over 15 years since the subject´s first clinical event | 
| Annualized relapse rate |  | Over 15 years since the subject´s first clinical event | 
| Time to conversion to Clinically-Definite Multiple Sclerosis (CDMS) |  | Over 15 years since the subject´s first clinical event | 
| Time to conversion to Secondary Progressive Multiple Sclerosis (SPMS) |  | Over 15 years since the subject´s first clinical event | 
| Expanded Disability Status Scale these scores (EDSS score) for disability assessed by the investigator during the neurological examination |  | 15 years after the subject´s first clinical event | 
| Number of subjects with confirmed and sustained 1-point EDSS progression (Disability progression) |  | Over 15 years since the subject´s first clinical event | 
| Number of subjects with confirmed 2.5-point EDSS progression (Disability progression) |  | Over 15 years since the subject´s first clinical event | 
| Multiple Sclerosis Functional Composite (MSFC) score (Neurological status) | MSFC: Multiple Sclerosis Functional Composite | Over 15 years since the subject´s first clinical event | 
| Paced Auditory Serial Addition Test (PASAT-3) score (Cognitive function) |  | Over 15 years since the subject´s first clinical event | 
| Time to use of ambulatory device |  | Over 15 years since the subject´s first clinical event | 
| Time to dependence on ambulatory device |  | Over 15 years since the subject´s first clinical event | 
| Time to use of wheelchair |  | Over 15 years since the subject´s first clinical event | 
| Employment status (Standardized questions) | The current employment will be recorded | At one single visit, 15 years after the subject's first clinical event | 
| Multiple sclerosis impact on employment |  | At one single visit, 15 years after the subject's first clinical event | 
| Resource use assessment questions: Help from family/regular ambulatory services |  | At one single visit, 15 years after the subject's first clinical event | 
| Resource use assessment questions: Additional ambulatory services during relapse |  | At one single visit, 15 years after the subject's first clinical event | 
| Resource use assessment questions: Adaptions (past 6 months) |  | At one single visit, 15 years after the subject's first clinical event | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symbol Digit Modalities Test score (SDMT score) | SDMT: Symbol Digit Modalities Test, Cognitive test For sustained attention, concentration and information processing speed | At one single visit, 15 years after the subject's first clinical event | 
| Relation of SDMT and FSMC (Fatigue Scale for Motor and Cognitive Functions) |  | At one single visit, 15 years after the subject's first clinical event | 
| Relation of mental processing speed and MRI parameters |  | At one single visit, 15 years after the subject's first clinical event | 
| European Quality of life - 5 Dimensions Health-related Quality of life (EQ-5D HRQoL) score | EQ-5D: European Quality of Life - 5 dimensions Questionnaire measuring health-related quality of life | Over 15 years since the subject´s first clinical event | 
| European Quality of Life-5 Dimensions Visual Analog Scale (EQ-5D VAS) score |  | Over 15 years since the subject's first clinical event | 
| Functional Assessment of Multiple Sclerosis (FAMS score) | FAMS: Functional Assessment of Multiple Sclerosis Questionnaire measuring health-related quality of life | Over 15 years since the subject´s first clinical event | 
| Fatigue Scale for Motor and Cognitive Functions (FSMC score) |  | At one single visit, 15 years after the subject's first clinical event | 
| Center of Epidemiological Studies for Depression (CES-D) score |  | At one single visit, 15 years after the subject's first clinical event | 
| Time to second line therapy |  | Over 15 years since the subject´s first clinical event | 
| Time to first disease-modifying therapies (DMT) other than IFNB-1b |  | Over 15 years since the subject´s first clinical event | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinically Isolated Syndrome suggestive of Multiple Sclerosis or Multiple Sclerosis