Cyclic Oral Methylprednisolone Trial in Multiple Sclerosis (COMTiMS)
The purpose of this study is to determine whether cyclic oral methylprednisolone once every month has an effect on the intrathecal inflammation in patients suffering from progressive multiple sclerosis.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Cyclic Oral Methylprednisolone Trial in Multiple Sclerosis|
- CSF osteopontin [ Time Frame: baseline and week 60 ] [ Designated as safety issue: No ]
- aims for clinical progression [ Time Frame: baseline and week 60 ] [ Designated as safety issue: No ]
- Change in expanded disability status scale (EDSS)
- Change in Timed 25-foot Walk (T25FW)
- Change in Multiple sclerosis impairment scale (MSIS)
- Change in multiple sclerosis functional composite (MSFC)
- Change in short form 36 (SF-36)
- aims for demyelination and disease activity [ Time Frame: baseline, week 12 (only MRI aims and MEP) and week 60 ] [ Designated as safety issue: No ]1. Change in the concentration of neurofilament heavy chain (NfH) in CSF 2. Change in the concentration of myelin basic protein (MBP) i CSF 3. Change in normalised brain volume (NBV), grey matter volume (GMV) og white matter volume (WMV) 4. Change in MTR og DTI i hele hjernen, lesions, normal appearing grey matter (NAGM) og normal appearing white matter (NAWM) 5. MEP (motor evoked potentials)
- aims of intrathecal inflammation [ Time Frame: baseline and week 60 ] [ Designated as safety issue: No ]
- Change in cellcount i CSF
- Change in IgG-index
- Change in the concentration of nitric oxid (NO) metabolittes in CSV
- Change in CSV-serum albumin qvotient
- Change in the concentration of CXCL13 i CSF
- Change in the concentration of MMP-9 i CSF
- Number of new Gd-enhancing lessions on MRI
- Volume of T2 lessions on MRI
- Number of new or bigger T2 lessions on
- Change in MTR in the hole brain, in lessions, grey matter og white matter
- Change in DTI the hole brain, in lessions, grey matter og white matter
- safety [ Time Frame: screnning, baseline, week 12, 24, 36, 48, 60 ] [ Designated as safety issue: Yes ]physical examination, blood pressure, pulse, DEXA scan, bloodtests
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||August 2013|
|Estimated Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
all patients will be treated with the active drug methylprednisolone 500 mg in 3 days every month for 60 weeks.
500 mg of methylprednisolone taken in 3 days every month
Other Name: Medrol
Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). It is presumably T-cell mediated and it is the most common non-traumatic cause of disability affecting young people. 85 % of the MS causes starts out as relapsing remitting MS (RRMS) and 15 % as primary progressive MS (PPMS). It has been found that after 10 years 40-45 % of the RRMS patients will convert to a more progressive state of disease, secondary progressive MS (SPMS).
Until recently it has been believed that the progression seen in MS occurred because of axonal loss and neurodegeneration could occur independently of inflammation. Now neuropathology studies shows that there is a close association between inflammation and neurodegeneration in all stages of MS - also the progressive forms of MS.
Osteopontin (OPN) is an extracellular matrix protein with chemokine, cytokine and intergrin properties. It has multiple immunological functions and is secreted by activated macrophages, leukocytes and activated T lymphocytes. It is present in extracellular fluids and is up-regulated at sites of inflammation. Increased levels of OPN where reported in the cerebrospinal fluid (CSF) in patients with MS.
The main aim of this study is to analyze the effect of cyclic oral methylprednisolone on the intrathecal inflammation in patients suffering from progressive multiple sclerosis measured by OPN in the CSF. Second the investigators will look at other aims of intrathecal inflammation, neurodegeneration, demyelination and safety.
|Copenhagen, Denmark, 2100|
|Principal Investigator:||Rikke Ratzer, MD||Scleroseklinikken, Rigshospitalet|
|Study Chair:||Per S Sørensen, Professor, MD||Scleroseklinikken, Rigshospitalet|