Cyclic Oral Methylprednisolone Trial in Multiple Sclerosis (COMTiMS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01305837
Recruitment Status : Completed
First Posted : March 1, 2011
Last Update Posted : July 11, 2013
Information provided by (Responsible Party):
Rikke Ratzer, Rigshospitalet, Denmark

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Progressive Multiple Sclerosis Drug: methylprednisolone Phase 2

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cyclic Oral Methylprednisolone Trial in Multiple Sclerosis
Study Start Date : April 2011
Actual Primary Completion Date : July 2013
Actual Study Completion Date : July 2013

Arm Intervention/treatment
Experimental: methylprednisolone
all patients will be treated with the active drug methylprednisolone 500 mg in 3 days every month for 60 weeks.
Drug: methylprednisolone
500 mg of methylprednisolone taken in 3 days every month
Other Name: Medrol

Primary Outcome Measures :
  1. CSF osteopontin [ Time Frame: baseline and week 60 ]

Secondary Outcome Measures :
  1. aims for clinical progression [ Time Frame: baseline and week 60 ]
    1. Change in expanded disability status scale (EDSS)
    2. Change in Timed 25-foot Walk (T25FW)
    3. Change in Multiple sclerosis impairment scale (MSIS)
    4. Change in multiple sclerosis functional composite (MSFC)
    5. Change in short form 36 (SF-36)

  2. aims for demyelination and disease activity [ Time Frame: baseline, week 12 (only MRI aims and MEP) and week 60 ]
    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)

  3. aims of intrathecal inflammation [ Time Frame: baseline and week 60 ]
    1. Change in cellcount i CSF
    2. Change in IgG-index
    3. Change in the concentration of nitric oxid (NO) metabolittes in CSV
    4. Change in CSV-serum albumin qvotient
    5. Change in the concentration of CXCL13 i CSF
    6. Change in the concentration of MMP-9 i CSF
    7. Number of new Gd-enhancing lessions on MRI
    8. Volume of T2 lessions on MRI
    9. Number of new or bigger T2 lessions on
    10. Change in MTR in the hole brain, in lessions, grey matter og white matter
    11. Change in DTI the hole brain, in lessions, grey matter og white matter

  4. safety [ Time Frame: screnning, baseline, week 12, 24, 36, 48, 60 ]
    physical examination, blood pressure, pulse, DEXA scan, bloodtests

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age between 18 and 65 years old
  • Progressive form of MS (Eg. primary or secondary progressive MS)
  • Duration of progressive phase at least 1 year
  • Progression of at least 1 EDSS point for the last 2 years or at least ½ EDSS point in patients with EDSS > 5,5
  • Progressin in 2 FS point
  • EDSS </= 6,5
  • Signed informed consent and written authority

Exclusion Criteria:

  • Pregnancy and breast feeding
  • Lack of secure contraception for women of child-bearing age (hormonal or intrauterine device)
  • Attack in the last month previous to inclusion
  • Treatment with methylprednisolone or cyclic methylprednisolone the 3 previous month before inclusion
  • Treatment with interferon-beta, Glatiramer acetate, immunglobulin G or other immunomodulating treatment the 3 previous month before inclusion
  • Treatment with Mitoxantrone, ciclofosfamide, Azathioprin or other immunosuppressive treatment the 6 previous month before inclusion
  • Previous treatment with drugs which the treating physician finds could have influence on the study results
  • Diseases associated with immune defects
  • Treatment with other anticoagulant than acetyl salicyl acid
  • Malignancy
  • Diabetes Mellitus
  • Renal insufficiency or S-Creatinine > 150 mmol/l
  • Acute or chronic infections with hepatitis B og C virus, HIV or other infections which the treating physician finds relevant
  • Psychiatric illness or other conditions which can impair the collaboration of the patient participating in the study
  • Contra-indication to MRI
  • Hypersensitivity to methylprednisolone
  • Osteoporosis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01305837

Scleroseklinikken, Rigshospitalet
Copenhagen, Denmark, 2100
Sponsors and Collaborators
Rigshospitalet, Denmark
Principal Investigator: Rikke Ratzer, MD Scleroseklinikken, Rigshospitalet
Study Chair: Per S Sørensen, Professor, MD Scleroseklinikken, Rigshospitalet

Responsible Party: Rikke Ratzer, MD, Rigshospitalet, Denmark Identifier: NCT01305837     History of Changes
Other Study ID Numbers: 2010-370
2010-024561-43 ( EudraCT Number )
First Posted: March 1, 2011    Key Record Dates
Last Update Posted: July 11, 2013
Last Verified: July 2013

Keywords provided by Rikke Ratzer, Rigshospitalet, Denmark:
multiple sclerosis

Additional relevant MeSH terms:
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents