Natalizumab and Chronic Inflammation

Study Overview
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Brief Summary
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In this study the investigators will assess the ability of Natalizumab, a medication given to treat multiple sclerosis (MS), to restore blood brain barrier integrity and repair subtle leakages of the blood brain barrier (BBB).

Detailed Description
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The investigators will image a cohort of persons with relapsing remitting multiple sclerosis (pwRRMS) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and selective inversion recovery quantitative magnetization transfer imaging (SIR-qMT). pwRRMS will be imaged at baseline and at month-3 and month-12, after starting treatment with natalizumab. Changes in ktrans, a measure of BBB permeability derived from DCE-MRI, and in pool saturation ratio (PSR) a measure of myelin integrity derived from SIR-qMT will be computed to assess the ability of natalizumab to fully restore BBB integrity. As a corollary aim, the investigators will assess changes in quality of life (QoL) measurements and the relation between those measurements and those derived from the above detailed quantitative MRI methods. QoL will be measured using the Visual Analogue Scale. This questionnaire entails 13 questions regarding the perceived effect of Tysabri, but also level of pain, fatigue, anxiety, depression before and during treatment with natalizumab. The answer to each question is rated on a color-coded bar the range of which is between 0 to 100.

Official Title
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Assessing the Effect of Natalizumab of Magnetic Resonance Imaging Measures of Blood Brain Barrier Permeability and Myelin Integrity

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Natalizumab 300 MG in 15 ML Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: multiple sclerosis clinical eligibility to treatment with Natalizumab no previous exposure to Natalizumab treatment Exclusion Criteria: inability to perform an MRI with contrast inability to undergo a paper-pencil questionnaires and blood work

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, prospective longitudinal study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment Single Arm<br>SINGLE ARM: 30 patients with multiple sclerosis treated with Natlizumab infusion given monthly at the dose of 300 mg IV | Drug: Natalizumab 300 MG in 15 ML Injection<br>* Disease modifying agent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Natalizumab on magnetic resonance imaging measures of blood brain barrier permeability: K-trans | To measure changes in k-trans between baseline (pre-treatment) and month-3 and month-12 post-treatment scan | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Natalizumab on magnetic resonance imaging measures of myelin integrity: pool saturation ratio (PSR) | To measure changes in PSR between baseline (pre-treatment) and month-3 and month-12 post-treatment scan | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple sclerosis, MRI, blood brain barrier, myelin