Clinical trial NCT01305837: Cyclic Oral Methylprednisolone Trial in Multiple Sclerosis
Official title: Cyclic Oral Methylprednisolone Trial in Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Progressive Multiple Sclerosis
Keywords: multiple sclerosis
methylprednisolone
osteopontin
inflammation
demyelinating
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2011-03-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: CSF osteopontin
timeFrame: baseline and week 60
Secondary outcomes:
measure: aims for clinical progression
timeFrame: baseline and week 60
measure: aims for demyelination and disease activity
timeFrame: baseline, week 12 (only MRI aims and MEP) and week 60
measure: aims of intrathecal inflammation
timeFrame: baseline and week 60
measure: safety
timeFrame: screnning, baseline, week 12, 24, 36, 48, 60
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Scleroseklinikken, Rigshospitalet
Study officials:
affiliation: Scleroseklinikken, Rigshospitalet
name: Rikke Ratzer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Scleroseklinikken, Rigshospitalet
name: Per S Sørensen, Professor, MD
role: STUDY_CHAIR
References: