Cyclic Oral Methylprednisolone Trial in Multiple Sclerosis

Progressive Multiple Sclerosis Clinical Trial

— COMTiMS  

Official title:

Cyclic Oral Methylprednisolone Trial in Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01305837
• Other study ID #: 2010-370
• Secondary ID: 2010-024561-43
• Status: Completed
• Phase: Phase 2
• First received: February 28, 2011
• Last updated: July 10, 2013
• Start date: April 2011
• Est. completion date: July 2013

Study information

• Verified date: July 2013
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Progressive Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• methylprednisolone
500 mg of methylprednisolone taken in 3 days every month

Locations

Country	Name	City	State
Denmark	Scleroseklinikken, Rigshospitalet	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CSF osteopontin		baseline and week 60	No
Secondary	aims for clinical progression	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)	baseline and week 60	No
Secondary	aims for demyelination and disease activity	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)	baseline, week 12 (only MRI aims and MEP) and week 60	No
Secondary	aims of intrathecal inflammation	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	baseline and week 60	No
Secondary	safety	physical examination, blood pressure, pulse, DEXA scan, bloodtests	screnning, baseline, week 12, 24, 36, 48, 60	Yes