Optic Neuritis
Conditions
Keywords
Optic Neuritis, Vitamin D
Brief summary
This is a phase II randomized double-blind placebo/standard of care trial to determine if rapidly inducing vitamin D sufficiency in patients with acute optic neuritis results in less damage/greater recovery at 12 months as measured by optical coherence tomography, visual evoked potentials, visual acuity and radiological measures. Our hypothesis, based on earlier observational studies, is that acute optic neuritis in the context of vitamin D sufficiency results in better visual outcomes compared to those that are not sufficient acutely, regardless of such interventions as steroid therapy.
Detailed description
The present trial is based on the observation that vitamin D sufficiency appears to provide some degree of neuroprotection and/or repair in the context of an acute optic neuritis when followed over several months using optical coherence tomography measures. Based on these findings, this randomized double-blinded placebo/standard of care controlled trial has been designed to to see if rapidly inducing vitamin D sufficiency (defined in this trial as a serum 25(OH)D value =\> 80 nmol/L) results in relatively less reduction in neuroaxonal injury and/or improved recovery chronically (at month 12) versus those patients who do not achieve vitamin D sufficiency in the acute optic neuritis period. of Vitamin D. In this trial, 66 patients in total will be randomized to either high-dose vitamin D induction treatment group or the placebo/followed by standard of care vitamin D group and followed over 12 months.The primary measure of neuroaxonal integrity in this trial is optical coherence tomography outcomes including ganglion cell layer thickness, retinal nerve fiber layer thickness and macular volume. Other vision metrics and magnetic resonance imaging (MRI) measures will provide secondary outcome indicators of this as well.
Interventions
DRUGVitamin D3
50,000 IU/d of oral vitamin D3 x 5 days followed by 10,000 IU/d of oral vitamin D3 x 85 days
DRUGPlacebo/Standard of Care Vitamin D3
50,000 IU/d of oral vitamin D3 x 5 days followed by 40,000 IU/d of oral vitamin D3 x 85 days
Sponsors
University of Calgary
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Masked randomization and allocation, only data safety monitor will know allocation if adverse event requires unblinding
Intervention model description
A double-blind randomized placebo/standard therapy phase II trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Canadian residents * Patients must be between age 18 and 45 years * Patients must have a diagnosis of either a CIS or RRMS (according to McDonald criteria) * Patients must have an EDSS of 5.5 or less * Patients must demonstrate features of a first typical optic neuritis within 21 days of recruitment (or must initiate treatment by day 30) * Patients must have a baseline 25(OH)D \< 80 nmol/L regardless of vitamin D3 supplementation * Patients must have no contraindications to high-dose vitamin D supplementation * Female patients must consent to use a reliable form of contraception (oral contraceptive pill, intrauterine device, barrier methods, abstinence) for the duration of the active treatment phase (first 90 days of where study drug provided) of the trial * Patients must provide written informed consent.
Exclusion criteria
* Patients who have had a previous optic neuritis * Patients with evidence of a non-inflammatory cause of optic neuropathy * Patients with evidence of neuromyelitis optica spectrum disorder or NMOSD (i.e. bilateral optic neuritis, MRI evidence of longitudinally enhancing lesions involving the optic nerves (involving three or more segments of the optic nerve), and/or involving the optic chiasm, and optic tracts * Patients with a 25(OH)D \> 80 nmol/L
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inter-eye (IED) ganglion cell layer thickness (GCL) | month 12 | The difference between the unaffected and affected eye GCL thickness between treatment and placebo group |
| Proportion of patients with GCL IED <= 8 microns | 12 months | The proportion of patients with unaffected and affected eye GCL thickness of \< = 8 microns between groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in mean RNFL IED between eyes over time | baseline to 12 months | Rate of change in mean RNFL and GCL thickness in affected eye over study between groups |
| Mean GCL thickness | baseline to 12 months | Mean GCL thickness at baseline between groups |
| Inter-eye RNFL thickness | baseline to 12 months | The difference between the unaffected and affected eye RNFL thickness at baseline between treatment and placebo groups |
| Inter-eye GCL thickness | baseline | The difference between the unaffected and affected eye GCL thickness at baseline between treatment and placebo groups |
| Mean macular volume (MV) | baseline | Mean MV at baseline between groups |
| Mean multifocal VEP (MfVEP) latency | 1 month | Mean MfVEP at month 1 between groups |
| Mean change high and low contrast visual acuity (LogMAR) | 12 months | Mean high and low contrast visual acuity (LogMAR) between groups at from baseline to month 12 |
| Correlation between baseline mean multifocal VEP latency and month-12 GCL, GCL inter-eye difference, RNFL and inter-eye RNFL difference between treatment and placebo groups | 12 months | Correlation coefficient calculation between mean multifocal VEP latency at baseline and mean GCL, GCL inter-eye difference and RNFL and inter-eye RNFL difference at month 12 between treatment and placebo groups |
| Change in mean GCL in affected eye over time | baseline to 12 months | Rate of change in mean GCL thickness in affected eye over study between groups |
| Change in mean GCL IED between eyes over time | baseline to 12 months | Rate of change in mean GCL IED thickness in affected eye over study between groups |
| Change in mean retinal nerve fiber layer (RNFL) in affected eye over time | baseline to 12 months | Rate of change in mean RNFL thickness in affected eye over study between groups |
| Change in mean RNFL in affected eye over time | baseline to 12 months | Rate of change in mean RNFL thickness in affected eye over study by 25(OH)D level |
| Mean RNFL thickness | baseline | Mean RNFL thickness at baseline and months between groups |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory novel MRI outcomes - diffusion tensor imaging (DTI) | 12 months | Changes in optic nerve, tract and radiations DTI between groups over study |
| Exploratory novel MRI outcomes - texture | 12 months | Changes in optic nerve, tract and radiations texture between groups over study |
| Exploratory novel MRI outcomes - cross-sectional area | 12 months | Changes in optic nerve, tract and radiations cross-sectional area between groups over study |
| Thalamic volume on MRI | 12 months | Mean thalamic volume over study between groups |
| New T2 brain lesions on MRI | 12 months | Mean number of new T2 lesions over study between groups |
| Conversion to clinically definite MS (CDMS) | 12 months | Proportion of patients with clinically isolated syndromes (CIS) who convert to CDMS between groups |
| New contrast enhancing brain lesions on MRI | 12 months | Mean number of new contrast enhancing lesions over study between groups |
Countries
Canada
Outcome results
None listed