Cyclic Oral Methylprednisolone Trial in Multiple Sclerosis (COMTiMS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Rikke Ratzer, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01305837
First received: February 28, 2011
Last updated: July 10, 2013
Last verified: July 2013
  Purpose

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 Intervention Phase
Progressive Multiple Sclerosis
Drug: methylprednisolone
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • CSF osteopontin [ Time Frame: baseline and week 60 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • aims for clinical progression [ Time Frame: baseline and week 60 ] [ Designated as safety issue: No ]
    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)

  • 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 ]
    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

  • safety [ Time Frame: screnning, baseline, week 12, 24, 36, 48, 60 ] [ Designated as safety issue: Yes ]
    physical examination, blood pressure, pulse, DEXA scan, bloodtests


Enrollment: 30
Study Start Date: April 2011
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01305837

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

No publications provided

Responsible Party: Rikke Ratzer, MD, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01305837     History of Changes
Other Study ID Numbers: 2010-370, 2010-024561-43
Study First Received: February 28, 2011
Last Updated: July 10, 2013
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by Rigshospitalet, Denmark:
multiple sclerosis
methylprednisolone
osteopontin
inflammation
demyelinating

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

ClinicalTrials.gov processed this record on July 22, 2014