Clinical trial NCT01077466: Natalizumab Treatment of Progressive Multiple Sclerosis
Official title: Natalizumab Treatment of Progressive Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Progressive Multiple Sclerosis
Secondary Progressive Multiple Sclerosis
Keywords: Primary Progressive Multiple Sclerosis
Secondary Progressive Multiple Sclerosis
Natalizumab
Treatment
Safety
Efficacy
Cerebrospinal fluid
Osteopontin
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Copenhagen University Hospital, Hvidovre
name: Biogen
name: University of Copenhagen
name: Signifikans ApS
First posted: 2010-03-01
Enrollment: 24
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to study safety and efficacy of natalizumab treatment of primary and secondary progressive multiple sclerosis.

This will be done by measuring the effect of treatment on inflammation in the CNS by means of osteopontin levels in the cerebrospinal fluid (CSF). Safety measures further includes physical and neurological examination,blood samples and MRI measures of disease activity.

Detailed description: The study will include 12 secondary progressive multiple sclerosis patients and 12 primary progressive multiple sclerosis patients to treatment with IV natalizumab for 60 weeks. At baseline and week 60 a lumbar puncture will be performed. MRI scans will be performed at baseline week 12 and week 60.Safety blood samples will be collected every 12 week.

Eligibility criteria: Inclusion Criteria:

* Age between 19 and 55 years
* Progressive disease course of multiple sclerosis (primary or secondary)
* Duration of progressive phase of at least 1 year
* Progression of \> 1 EDSS point during the last 2 years (\>½ EDSS point if EDSS \> 5,5)
* EDSS \</= 6.5
* Written and informed consent

Exclusion Criteria:

* Pregnancy, breast-feeding or lack of anti.conception for fertile women.
* Attack during the last month before inclusion.
* Treatment with methylprednisolone during 3 months before inclusion.
* Treatment with interferon-beta, glatirameracetate, immunoglobulin G or other immune-modulating treatment 3 months prior to inclusion.
* Treatment with mitoxantrone, cyclophosphamide, azathioprine or other strong immunosuppressive drug 6 months prior to inclusion.
* Prior experimental treatment with strong immunosuppressive drug which the treating physician means will influence the results of the trial.
* Diseases associated with immunodeficiency.
* Treatment with other anticoagulant than aspirin.
* Current malign disease.
* Diabetes Mellitus or other autoimmune disease.
* Renal insufficiency or creatinine \> 150 μmol/l.
* Travel in tropical areas 3 months prior to inclusion.
* Acute or chronic infectious diseases, which the treating physician finds relevant (e.g.hepatitis B virus, hepatitis C virus, HIV).
* Psychiatric disease or other circumstances that may limit the patients participation in the trial.
* Contraindication for MRI scan or gadolinium contrast .
* Known hypersensitivity to natalizumab.

Primary outcomes:
measure: Cerebrospinal fluid (CSF) osteopontin
timeFrame: Change from baseline to week 60
Secondary outcomes:
measure: Expanded disability status scale (EDSS)
timeFrame: Baseline to week 60
measure: Timed 25-foot Walk (T25FW)
timeFrame: Baseline to week 60
measure: Multiple Sclerosis Impairment Score (MSIS)
timeFrame: Baseline to week 60
measure: Multiple Sclerosis Functional Composite
timeFrame: Baseline to week 60
measure: Short Form 36 Health Survey (SF36)
timeFrame: Baseline to week 60
measure: CSF Neurofilament Heavy Chain
timeFrame: Baseline to week 60
measure: CSF Myelin Basic Protein
timeFrame: Baseline to week 60
measure: Atrophy
timeFrame: Week 12 to week 60
measure: Magnetization transfer ratio (MTR)
timeFrame: Baseline to week 60
measure: Diffusion transfer imaging (DTI)
timeFrame: Baseline to week 60
measure: CSF cell count
timeFrame: Baseline to week 60
measure: Change in IgG-index
timeFrame: Baseline to week 60
measure: CSF nitrogen oxide metabolites
timeFrame: Baseline to week 60
measure: CSF-serum albumine concentration quotient
timeFrame: Baseline to week 60
measure: CSF CXCL13
timeFrame: Baseline to week 60
measure: Matrix metalloproteinase-9 (MMP-9)
timeFrame: Baseline to week 60
measure: New Gadolinium-enhancing lesions (GdEL)
timeFrame: Baseline to week 60
measure: Volume of lesions on T2-weighted MRI images
timeFrame: Baseline to week 60
measure: Number of new or enlarging lesions on T2-weighted MRI images
timeFrame: Baseline to week 60
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Danish Multiple Sclerosis Center, Section 2082, Rigshospitalet
Study officials:
affiliation: Danish Multiple Sclerosis Center
name: Finn Sellebjerg, MD PhD DMSc
role: PRINCIPAL_INVESTIGATOR
References: