Myelitis, Myelitis, Transverse, Optic Neuritis
Conditions
Keywords
Plasma Exchange, Plasmapheresis, Apheresis, Pheresis
Brief summary
The purpose of this research is to evaluate if early vs rescue Therapeutic Plasma Exchange (PLEX) treatment algorithm leads to better visual outcomes in severe Optic Neuritis and leads to better neurological disability outcomes in severe Transverse Myelitis.
Interventions
DRUGHigh-dose corticosteroids (HDCS)
Subjects will receive initial treatment with high-dose corticosteroids (HDCS) in the form of methylprednisolone (1,000mg daily) administered intravenously for 5 days or a bioequivalent dose of oral corticosteroids (e.g., 1,250mg prednisone daily or 176mg dexamethasone daily). Subjects will be escalated to PLEX if there is an insufficient response to HDCS (decision point at 14±2 days for the ON sub-trial and 7±2 days for the TM sub-trial) PLEX will be performed as 5 sessions over 5-10 days, with 1-1.5 plasma volumes exchanged per session.
DRUGHigh-dose corticosteroids (HDCS) and PLEX
Subjects will receive treatment with high-dose corticosteroids (HDCS) and PLEX initiated concurrently. HDCS will be administered in the form of methylprednisolone (1,000mg daily) administered intravenously for 5 days or a bioequivalent dose of oral corticosteroids (e.g., 1,250mg prednisone daily or 176mg dexamethasone daily). PLEX will be performed as 5 sessions over 5-10 days, with 1-1.5 plasma volumes exchanged per session.
Sponsors
Mayo Clinic
Patient-Centered Outcomes Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Study Population and Setting The proposal will recruit participants presenting to participating sites with severe ON or severe TM to two separate sub-trials. The detailed inclusion and
Exclusion criteria
for each sub-trial are listed below: Optic Neuritis Sub-Trial: Inclusion criteria: * ≥18 years of age * MRI orbits demonstrating evidence of new T2 hyperintensity and/or post-gadolinium contrast enhancement of the optic nerve(s) and meeting the clinical criteria for Optic Neuritis * Visual acuity 20/200 or worse * Within 8 days of onset of visual symptoms * Able to initiate PLEX within 72h of the first dose of HDCS (if randomized to the "Early PLEX" treatment arm) * Able to sign and date informed consent form * Willingness to comply with all study procedures and availability for the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| High contrast visual acuity | 6 months | The Optic Neuritis subjects will have high contrast visual acuity measured by ETDRS 100% high-contrast Sloan letter charts. A high contrast visual acuity of 20/20 is considered "normal," a high contrast visual acuity of 20/40 or better is required to be able to drive without restrictions, and a high contrast visual acuity of 20/200 or worse is considered legally blind. |
| Expanded Disability Status Score (EDSS) | 6 months | The level of disability in Transverse Myelitis subjects will be assessed using the Expanded Disability Status Scale (EDSS). The EDSS assesses various neurological functional systems, including pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, and cereberal functions and ranges from 0 (normal neurological examination) to 10 (death). Higher scores indicate greater disability. Visual and cerebral functional system scores will be excluded from the EDSS calculation for quantification of Transverse Myelitis-related disability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Low contrast (2.5%) visual acuity | 6 months | Optic Neuritis subjects will have low contrast visual acuity (best corrected) assessed with 2.5% low-contrast Sloan letter charts |
| Peri-papillary retinal nerve fiber layer (RNFL thickness) | 6 months | Optic Neuritis subjects will have RNFL thickness measured via Retinal Optical Coherence Tomography (OCT). |
| Macular ganglion cell-inner plexiform layer (GCIPL) thicknesses | 6 months | Optic Neuritis subjects will have GCIPL thickness measured via Retinal Optical Coherence Tomography (OCT). |
| Hardy Rand and Rittler (HRR) color plates | 6 months | The Hardy-Rand-Rittler (HRR) color plates test will be administered to Optic Neuritis subjects. The HRR is scored based on the number of correct responses to the diagnostic plates, with the total number of correct figures out of 28 being the primary score. |
| National Eye Institute (NEI) 10-Item Neuro-Ophthalmic Supplement | 6 months | Optic Neuritis subjects will complete the 10-Item Neuro-Ophthalmic Supplement, a 10-item questionnaire used to assess visual dysfunction in patients with neuro-ophthalmologic disorders. It is scored on a scale of 0 to 100, with higher scores indicating better visual functioning. |
| Ambulatory disability | 6 months | Transverse Myelitis subjects will be assessed for ambulatory disability using the Hauser Ambulation Index, a timed 25 foot, 6 minute walk. |
| Manual dexterity (Nine-Hole Peg Test) | 6 months | The Nine-Hole Peg Test will be administered to the Transverse Myelitis subjects. Subjects will be asked to take the pegs from a container, one by one, and place them into holes on the board as quickly as possible. They will then remove the pegs, one by one, from the board as quickly as possible. Scores are based on the time taken to complete the activity and are reported in seconds. |
| Patient Determined Disease Steps (PDDS) | 6 months | Transverse Myelitis subjects will complete the Patient-Determined Disease Steps (PDDS), a self-reported disability scale with 9 levels ranging from no disability to bedridden. |
| Spinal Cord Injury Quality of Life questionnaire (SCI-QoL) | 6 months | Transverse Myelitis subjects will complete the The Spinal Cord Injury Quality of Life questionnaire (SCI-QoL), which includes assessments of specific domains related to bladder/bowel dysfunction, pain, pressure ulcers, mobility/ambulation, fine motor skills, self-care, and wheelchair mobility. |
| PLEX Complications | 2 weeks, 1 month | Total number of adverse events categorized according to the Common Terminology Criteria for Adverse Events v5.0 |
| National Eye Institute (NEI) Visual Function Questionnaire (VFQ)-25 | 6 months | Optic Neuritis subjects will complete the National Eye Institute Visual Functioning Questionnaire-25. The questionnaire consists of 25 items, covering 11 vision-related domains, plus a single global-rating item. Items are scored and converted to a 0- to 100-point scale where higher scores indicate better functioning. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJohn Chen
Mayo Clinic
Outcome results
None listed