Study to Evaluate Intravenous and Oral Steroids for Multiple Sclerosis Attacks

Intravenous methylprednisolone has been the standard of care for treating acute MS flares. However, the IV administration is cumbersome, inconvenient and expensive. A true comparison of these different approaches has not been undertaken in rigorous fashion. Prior studies have demonstrated the safety of such high doses of oral steroid. For this proposal we employ equivalent oral dosing (1400 mg/day) and compare that to 1000 mg/day IV therapy in patients seen within seven days of an acute exacerbation of MS.

In addition, there are 2 arms to this double-blind, placebo controlled, randomized trial. One arm has an active IV and an oral placebo while the second arm has an IV placebo and an active oral dose. Therefore, each subject will receive an active treatment.

• megadose oral methylprednisolone (Drug): 1400 mg qd/5 days
• IV methylprednisolone (Drug): 1000 mg/qd/5 days

Primary outcomes

• Expanded Disability Status Scale (EDSS) Mean Recovery From Day 0 to Day 28. [Day 28 and Day 90]: There is no data analysis for this study

Secondary outcomes

• Clinical Parameters of the Multiple Sclerosis Functional Composite Scale (MSFC) Between Oral and IV Steroid Therapy in Subjects With Relapsing Forms of MS. [Day 28 and day 90]
• Frequency of Relapse Over Time (up to One Year) When Subjects With Relapsing Forms of MS Are Administered One Course of Oral Methylprednisolone Compared to IV Administration. [Day 28 and day 90 and day 365]
• Improvement Using Targeted Neurological Deficits (TND). [Day 28 and day 90]

Sex: All, ages: 18 Years to 50 Years

Inclusion Criteria:

* Between the ages of 18 and 50 years, inclusive.
* Acute symptomatic exacerbation of MS present for great than 24 hours and less than or equal to 7 days at entry with new or worsening symptoms, and with signs referable to the symptoms; in the absence of a fever or active infection.
* Diagnosis of a relapsing form of multiple sclerosis before randomization as determined by Poser or McDonald Criteria.
* Expanded disability status scale (EDSS) score between 2 and 6.5, inclusive at entry.
* Episodes include study neurologist or neuro-ophthalmologist diagnosed: acute optic neuritis, cerebellar, brainstem dysfunction, myelitis, focal cerebral, and/or definitive focal sensory dysfunction.
* New objective clinical finding other than a sensory exacerbation, or bowel/bladder signs alone. Sensory deficits alone will not qualify except for optic neuritis.
* Subjects may continue on their current immunomodulating therapy (such as interferons or glatiramer acetate) throughout the course of the study. Women who become pregnant after the 5-day treatment of steroids should discontinue immunomodulatory treatment.
* Understand and sign written informed consent prior to any testing under this protocol, including screening tests and evaluations that are not considered part of the subject's routine care.

Exclusion Criteria:

* Any patients treated with systemic corticosteroid use within one month of the index episode at screening.
* Prior use of immunosuppressive treatments within 90 days of index episode (mitoxantrone, azathioprine, IVIg) or plasmapheresis.
* Any patient who is pregnant or breastfeeding.
* Unable to perform the Multiple Sclerosis Functional Composite consisting of: Timed 25-Foot Walk, 9-Hole Peg Test, and Paced Auditory Serial Addition Test (3 second).
* Peripheral or cranial neuropathy as sole problem of acute episode.
* History of any significant cardiac, gastrointestinal, hepatic, pulmonary, or renal disease; immune deficiency; or other medical conditions that would preclude corticosteroid therapy.
* Primary Progressive Multiple Sclerosis (PPMS).
* Previous participation in this study.

Participant flow

Outcome results

• Expanded Disability Status Scale (EDSS) Mean Recovery From Day 0 to Day 28. (Primary)
• Clinical Parameters of the Multiple Sclerosis Functional Composite Scale (MSFC) Between Oral and IV Steroid Therapy in Subjects With Relapsing Forms of MS. (Secondary)
• Frequency of Relapse Over Time (up to One Year) When Subjects With Relapsing Forms of MS Are Administered One Course of Oral Methylprednisolone Compared to IV Administration. (Secondary)
• Improvement Using Targeted Neurological Deficits (TND). (Secondary)

Adverse events

Limitations and caveats: The trial was terminated due to difficulties obtaining drug and matching placebo and the inability to meet recruitment. There was no data analysis done for this trial due to low enrollment and data will not be meaningful.

• Fred Lublin, MD, Principal investigator, Icahn School of Medicine at Mount Sinai