Myelitis, Transverse, Neuromyelitis Optica
Conditions
Keywords
Clinical Trials Unit, Pediatric
Brief summary
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
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.
Interventions
DRUGIntravenous Immunoglobulin
Sponsors
King's College London
Barts and the London School of Medicine and Dentistry
Cardiff University
University College, London
King's College Hospital NHS Trust
Great Ormond Street Hospital for Children NHS Foundation Trust
Barts & The London NHS Trust
Alder Hey Children's NHS Foundation Trust
Walton Centre NHS Foundation Trust
Oxford University Hospitals NHS Trust
Birmingham Women's and Children's NHS Foundation Trust
University Hospital Birmingham NHS Foundation Trust
Cardiff and Vale University Health Board
North Bristol NHS Trust
University Hospitals Bristol and Weston NHS Foundation Trust
Manchester University NHS Foundation Trust
Northern Care Alliance NHS Foundation Trust
University Hospital Southampton NHS Foundation Trust
Newcastle-upon-Tyne Hospitals NHS Trust
Nottingham University Hospitals NHS Trust
NHS Lothian
Guy's and St Thomas' NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 2 points or greater improvement on the American Spinal Injury Association (ASIA) Impairment scale (classified A-E) | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Change in ASIA motor scale (0-100) and ASIA sensory scale (0-112) | 6 months |
Other
| Measure | Time frame |
|---|---|
| Paediatric Quality of Life Inventory™(PedsQL) Parent Report for Young Children (for patients aged 5-7 years at presentation) | 6 months |
| International SCI Pain Basic Data Set (for patients ages 13 years or over at presentation) | 6 months |
| Paediatric Quality of Life Inventory™ (PedsQL) Parent Report for Toddlers (for patients aged 2-4 years at presentation) | 6 months |
| International SCI Bladder/Bowel Data Set (for patients aged 13 years or over at presentation) | 6 months |
Countries
United Kingdom
Outcome results
None listed