Phase III Randomized, Double-Blind, Sham-Controlled Study of Plasma Exchange for Acute Severe Attacks of Inflammatory Demyelinating Disease Refractory to Intravenous Methylprednisolone

Study Overview
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Brief Summary
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OBJECTIVES: I. Evaluate the effectiveness of plasma exchange in the treatment of acute severe attacks of inflammatory demyelinating disease in patients who have failed intravenous steroid therapy.

Detailed Description
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PROTOCOL OUTLINE: This is a randomized, double-blind study. Patients are stratified by disease type; each stratum is randomized separately. The first group of patients receives a true plasma exchange using continuous-flow centrifugation with serum albumin and crystalloid replacement every 2 days for a total of 7 exchanges. The second group receives a sham plasma exchange with no centrifugation every 2 days for a total of 7 exchanges. Patients cross to the alternate therapy if there is less than a moderate improvement by day 14. The treatment decision is based on a blinded neurologic assessment. Concurrent corticosteroids and other immunosuppressants, and high-dose barbiturates are not allowed. Patients are followed at 1 and 6 months after the last exchange.

Conditions
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Acute Disseminated Encephalomyelitis, Devic's Syndrome, Marburg's Variant of Multiple Sclerosis, Balo's Concentric Sclerosis, Acute Transverse Myelitis

Intervention / Treatment
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* Procedure: Plasma exchange


Participation Criteria
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Eligibility Criteria
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PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Idiopathic inflammatory demyelinating syndrome, as follows: biopsy-proven if necessary - established diagnosis of multiple sclerosis (MS) using Poser criteria; acute disseminated encephalomyelitis; Marburg's variant of MS Balo's concentric sclerosis Eligible without biopsy: acute transverse myelitis; Devic's syndrome Acute neurologic deficit markedly affecting consciousness, language, or brainstem/spinal cord function, i.e., aphasia, paraplegia, coma, quadriplegia, hemiplegia, severe organic brain syndrome Deficit unresponsive to 5 days of high-dose intravenous methylprednisolone (MePRDL), as follows: deficit duration of 21 days to 3 months AND no improvement 14 days after beginning MePRDL OR deficit duration of 12 to 20 days AND continued deterioration after completion of MePRDL No chronically progressive demyelinating disease No HIV-associated demyelinating syndrome No progressive multifocal leukoencephalopathy No optic neuritis --Prior/Concurrent Therapy-- No more than 3 months of prior steroid therapy Failure on prior MePRDL required Minimum dose 7 mg/kg per day for 5 days At least 6 weeks since other immunosuppressives, e.g., cyclophosphamide, azathioprine, cyclosporine --Patient Characteristics-- Renal: Creatinine less than 1.5 mg/dL Cardiovascular: No hypovolemia; no infarction; no vasculitis; no other major systemic cardiovascular illness Pulmonary: No major respiratory illness Other: No infection, including hepatitis or human immunodeficiency virus; no recent intravenous drug abuse; no high-risk sexual behavior; no cardiac, cerebrovascular, or autonomic dysfunction that would increase risk of hypotension; no other major systemic illness that would preclude protocol therapy; no pregnant or nursing women; negative serum pregnancy test required of fertile women; effective contraception required

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Plasma exchange|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rare disease, Balo's concentric sclerosis, Devic's syndrome, Marburg's variant of multiple sclerosis, acute disseminated encephalomyelitis, acute transverse myelitis, multiple sclerosis, neurologic and psychiatric disorders