A Multicentre randomiSed Controlled TRial of IntraVEnous Immunoglobulin Versus Standard Therapy for Transverse Myelitis

Study Overview
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Brief Summary
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This multi-center randomized controlled trial evaluates if the addition of intravenous immunoglobulin to standard treatment of corticosteroids improves outcome in children and adults with first episode of Transverse Myelitis of Neuro-myelitis optica. Half of participants will receive corticosteroids alone, whilst the other half will receive corticosteroids plus intravenous immunoglobulin.

Detailed Description
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Transverse myelitis (TM) is a severe demyelinating condition predominantly affecting young people, which causes significant long-term disability in approximately one third. Current initial treatment is with corticosteroids, although evidence for their use is based on extrapolation from trials in adult multiple sclerosis relapses. In view of the severity of the condition, additional treatments have been trialed. Intravenous immunoglobulin (IVIG) is often used as second-line treatment in steroid-unresponsive central nervous system demyelination, although evidence for its efficacy is limited to small case series and case reports. Randomized controlled trials have demonstrated that IVIG reduces inflammation and enhances remyelination in a number of neurological conditions, although there have been no randomized controlled trials testing its use in adults and children with TM. This study will evaluate if additional and early treatment with IVIG is of extra benefit in TM when compared to the current standard therapy of intravenous steroids alone.

Official Title
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A Multicentre randomiSed Controlled TRial of IntraVEnous Immunoglobulin (IVIg) Versus Standard Therapy for the Treatment of Transverse Myelitis in Adults and Children

Conditions
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Myelitis, Transverse, Neuromyelitis Optica

Intervention / Treatment
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* Drug: Intravenous Methylprednisolone
* Drug: Intravenous Immunoglobulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of EITHER acute first onset transverse myelitis (using the TM Consortium Working Group 2002 criteria) - patients must fulfill all of the following criteria: Sensory, motor, or autonomic dysfunction attributable to spinal cord disease Bilateral signs and/or symptoms (not necessarily symmetric) Sensory level (except in young children <5 years where this is difficult to evaluate) Lack of MRI brain criteria consistent with multiple sclerosis Progression to nadir between 4 h and 21 days OR first presentation of neuromyelitis optica (using standardised criteria) - patients must fulfil both absolute criteria: Optic neuritis Acute myelitis, plus two out of three supportive criteria (as Aquaporin 4 antibody (AQP4) is often not available acutely, only the first two supportive criteria would be applied), Brain MRI not meeting criteria for Multiple Sclerosis (MS) at disease onset Spinal cord MRI with contiguous T2-weighted signal abnormality extending over three or more vertebral segments, indicating a relatively large lesion in the spinal cord AQP4 seropositive status ASIA Impairment Score of A-C Randomisation to occur no later than day 5 of steroids, and, if definitely known, within 21 days from symptom onset. Give assent (8-16 years)/consent to participate in the trial Exclusion Criteria: Contraindication to IVIG as stated in the summary of product characteristics (SmPC), or receiving IVIG for other reasons Previously known systemic autoimmune disease (e.g. systemic lupus erythematosus) or any evidence of systemic inflammation during current presentation. Direct infectious aetiology (e.g. varicella zoster) Previous episode of central nervous system (CNS) inflammatory demyelination Acute disseminated encephalomyelitis (ADEM) Other causes of myelopathy not thought to be due to myelitis (e.g. nutritional, ischaemic, tumour etc.) Other disease which would interfere with assessment of outcome measures Known pregnancy Circumstances which would prevent follow-up for 12 month

Ages Eligible for Study
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Minimum Age: 1 Year

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
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravenous Methylprednisolone<br>Paediatric patients - 30mg/kg or 500mg/m2 up to a maximum daily dose of 1g/day for 5 days. Adult patients - 1g/day for 5 days. | Drug: Intravenous Methylprednisolone<br> <br> |
| Experimental: Intravenous Immunoglobulin<br>Paediatric patients <41.2kg - total dose of 2g/kg in divided doses over 2 days. All other patients - total dose of 2g/kg in divided doses over 5 days. PLUS Intravenous Methylprednisolone Pediatric patients - 30mg/kg or 500mg/m2 up to a maximum daily dose of 1g/day for 5 days. Adult patients - 1g/day for 5 days. | Drug: Intravenous Methylprednisolone<br> <br> Drug: Intravenous Immunoglobulin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2 points or greater improvement on the American Spinal Injury Association (ASIA) Impairment scale (classified A-E) |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ASIA motor scale (0-100) and ASIA sensory scale (0-112) |  | 6 months | 
| Change in Kurtzke's expanded disability status scale (EDSS) measured with Neurostatus scoring |  | 6 months | 
| EQ-5D-Y (for patients aged 8-12 years at presentation) |  | 6 months | 
| EQ-5D-5L (for patients aged 13 years or over at presentation) |  | 6 months | 
| International Spinal Cord Injury (SCI) Quality of Life Basic Data Set (for patients aged 13 years or over at presentation) |  | 6 months | 
| Client Service Receipt Inventory (CSRI) |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical Trials Unit, Pediatric