High-Dose Vitamin D Induction in Optic Neuritis
- Conditions
- Optic Neuritis
- Interventions
- Drug: Placebo/Standard of Care Vitamin D3
- Registration Number
- NCT03302585
- Lead Sponsor
- University of Calgary
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 12
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description High-Dose Vitamin D Treatment Group Vitamin D3 Patients in this arm will receive: -5 days of high-dose oral vitamin D3 (50,000 IU daily x 5), followed by 85 days of moderate dose oral vitamin D3 (10,000 IU daily x 85 days) Placebo/Standard Vitamin D3 Group Placebo/Standard of Care Vitamin D3 Patients in this arm will receive Placebo/Standard of Care Vitamin D3: -5 days of placebo, followed by 85 days of standard of care dose of oral vitamin D3 (4,000 IU daily x 85 days)
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 by 25(OH)D level
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
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
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 by 25(OH)D level
Mean RNFL thickness 12 months Mean RNFL thickness at month 12 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 IED between eyes over time baseline to 12 months Rate of change in mean RNFL and GCL thickness in affected eye over study by 25(OH)D level
Inter-eye GCL thickness 12 months The difference between the unaffected and affected eye RNFL thickness between treatment and placebo groups
Mean macular volume (MV) 12 months Mean MV at month 12 between groups
Mean multifocal VEP (MfVEP) latency 1 month Mean MfVEP at month 1 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 GCL thickness 12 months Mean GCL thickness at month 12 between groups
Inter-eye RNFL thickness 12 months The difference between the unaffected and affected eye RNFL thickness at month 12 between treatment and placebo groups
Trial Locations
- Locations (1)
Foothills Medical Centre, University of Calgary
🇨🇦Calgary, Alberta, Canada