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Natalizumab Treatment of Progressive Multiple Sclerosis (NAPMS)

Primary Purpose

Primary Progressive Multiple Sclerosis, Secondary Progressive Multiple Sclerosis

Status
Completed
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Natalizumab
Sponsored by
Rigshospitalet, Denmark
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Progressive Multiple Sclerosis focused on measuring Primary Progressive Multiple Sclerosis, Secondary Progressive Multiple Sclerosis, Natalizumab, Treatment, Safety, Efficacy, Cerebrospinal fluid, Osteopontin

Eligibility Criteria

19 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Danish Multiple Sclerosis Center, Section 2082, Rigshospitalet

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Natalizumab

Arm Description

24 patients: 12 with secondary progressive multiple sclerosis 12 with primary progressive multiple sclerosis

Outcomes

Primary Outcome Measures

Cerebrospinal fluid (CSF) osteopontin
The primary endpoint is change in CSF osteopontin from baseline to week 60.

Secondary Outcome Measures

Expanded disability status scale (EDSS)
Change in expanded disability status scale (EDSS)from baseline to week 60
Timed 25-foot Walk (T25FW)
Multiple Sclerosis Impairment Score (MSIS)
Multiple Sclerosis Functional Composite
Short Form 36 Health Survey (SF36)
CSF Neurofilament Heavy Chain
Change in neurofilament heavy chain in the cerebrospinal fluid
CSF Myelin Basic Protein
Change in myelin basic protein in CSF from baseline to week 60
Atrophy
Change in normalised brain volume (NBV), grey matter volume (GMV) og white matter volume (WMV) from week 12 to week 60
Magnetization transfer ratio (MTR)
Change in MTR in whole brain, lesions, normal-appearing grey matter (NAGM) og normal-appearing white matter (NAWM) from baseline to week 60
Diffusion transfer imaging (DTI)
Change in FA and ADC in lesions, GM and NAWM between baseline and week 60.
CSF cell count
Change in CSF cell count from baseline to week 60
Change in IgG-index
CSF nitrogen oxide metabolites
CSF-serum albumine concentration quotient
CSF CXCL13
Matrix metalloproteinase-9 (MMP-9)
New Gadolinium-enhancing lesions (GdEL)
Volume of lesions on T2-weighted MRI images
Number of new or enlarging lesions on T2-weighted MRI images

Full Information

First Posted
February 26, 2010
Last Updated
February 15, 2012
Sponsor
Rigshospitalet, Denmark
Collaborators
Copenhagen University Hospital, Hvidovre, Biogen, University of Copenhagen, Signifikans ApS
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1. Study Identification

Unique Protocol Identification Number
NCT01077466
Brief Title
Natalizumab Treatment of Progressive Multiple Sclerosis
Acronym
NAPMS
Official Title
Natalizumab Treatment of Progressive Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2012
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rigshospitalet, Denmark
Collaborators
Copenhagen University Hospital, Hvidovre, Biogen, University of Copenhagen, Signifikans ApS

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Progressive Multiple Sclerosis, Secondary Progressive Multiple Sclerosis
Keywords
Primary Progressive Multiple Sclerosis, Secondary Progressive Multiple Sclerosis, Natalizumab, Treatment, Safety, Efficacy, Cerebrospinal fluid, Osteopontin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Natalizumab
Arm Type
Experimental
Arm Description
24 patients: 12 with secondary progressive multiple sclerosis 12 with primary progressive multiple sclerosis
Intervention Type
Drug
Intervention Name(s)
Natalizumab
Other Intervention Name(s)
Tysabri
Intervention Description
300 mg Natalizumab IV for every 4 week for 56 weeks (15 doses for every patient)
Primary Outcome Measure Information:
Title
Cerebrospinal fluid (CSF) osteopontin
Description
The primary endpoint is change in CSF osteopontin from baseline to week 60.
Time Frame
Change from baseline to week 60
Secondary Outcome Measure Information:
Title
Expanded disability status scale (EDSS)
Description
Change in expanded disability status scale (EDSS)from baseline to week 60
Time Frame
Baseline to week 60
Title
Timed 25-foot Walk (T25FW)
Time Frame
Baseline to week 60
Title
Multiple Sclerosis Impairment Score (MSIS)
Time Frame
Baseline to week 60
Title
Multiple Sclerosis Functional Composite
Time Frame
Baseline to week 60
Title
Short Form 36 Health Survey (SF36)
Time Frame
Baseline to week 60
Title
CSF Neurofilament Heavy Chain
Description
Change in neurofilament heavy chain in the cerebrospinal fluid
Time Frame
Baseline to week 60
Title
CSF Myelin Basic Protein
Description
Change in myelin basic protein in CSF from baseline to week 60
Time Frame
Baseline to week 60
Title
Atrophy
Description
Change in normalised brain volume (NBV), grey matter volume (GMV) og white matter volume (WMV) from week 12 to week 60
Time Frame
Week 12 to week 60
Title
Magnetization transfer ratio (MTR)
Description
Change in MTR in whole brain, lesions, normal-appearing grey matter (NAGM) og normal-appearing white matter (NAWM) from baseline to week 60
Time Frame
Baseline to week 60
Title
Diffusion transfer imaging (DTI)
Description
Change in FA and ADC in lesions, GM and NAWM between baseline and week 60.
Time Frame
Baseline to week 60
Title
CSF cell count
Description
Change in CSF cell count from baseline to week 60
Time Frame
Baseline to week 60
Title
Change in IgG-index
Time Frame
Baseline to week 60
Title
CSF nitrogen oxide metabolites
Time Frame
Baseline to week 60
Title
CSF-serum albumine concentration quotient
Time Frame
Baseline to week 60
Title
CSF CXCL13
Time Frame
Baseline to week 60
Title
Matrix metalloproteinase-9 (MMP-9)
Time Frame
Baseline to week 60
Title
New Gadolinium-enhancing lesions (GdEL)
Time Frame
Baseline to week 60
Title
Volume of lesions on T2-weighted MRI images
Time Frame
Baseline to week 60
Title
Number of new or enlarging lesions on T2-weighted MRI images
Time Frame
Baseline to week 60

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Finn Sellebjerg, MD PhD DMSc
Organizational Affiliation
Danish Multiple Sclerosis Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Danish Multiple Sclerosis Center, Section 2082, Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark

12. IPD Sharing Statement

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Natalizumab Treatment of Progressive Multiple Sclerosis

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