Cyclic Oral Methylprednisolone Trial in Multiple Sclerosis

Condition(s) targeted: Progressive Multiple Sclerosis

Intervention: methylprednisolone (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Rigshospitalet, Denmark

Official(s) and/or principal investigator(s):
Rikke Ratzer, MD, Principal Investigator, Affiliation: Scleroseklinikken, Rigshospitalet
Per S Sørensen, Professor, MD, Study Chair, Affiliation: Scleroseklinikken, Rigshospitalet

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.

Official title: Cyclic Oral Methylprednisolone Trial in Multiple Sclerosis

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: CSF osteopontin

Secondary outcome:

aims for clinical progression

aims for demyelination and disease activity

aims of intrathecal inflammation

safety

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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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

- 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

Scleroseklinikken, Rigshospitalet, Copenhagen 2100, Denmark

Starting date: April 2011
Last updated: July 10, 2013