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inability to meet recruitment goals
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High-Dose Vitamin D Treatment Group | Experimental | 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 Comparator | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vitamin D3 | Drug | 50,000 IU/d of oral vitamin D3 x 5 days followed by 10,000 IU/d of oral vitamin D3 x 85 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Inter-eye (IED) ganglion cell layer thickness (GCL) | The difference between the unaffected and affected eye GCL thickness between treatment and placebo group | month 12 |
| Proportion of patients with GCL IED <= 8 microns | The proportion of patients with unaffected and affected eye GCL thickness of < = 8 microns between groups | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in mean GCL in affected eye over time | Rate of change in mean GCL thickness in affected eye over study between groups | baseline to 12 months |
| Change in mean GCL in affected eye over time |
| Measure | Description | Time Frame |
|---|---|---|
| Conversion to clinically definite MS (CDMS) | Proportion of patients with clinically isolated syndromes (CIS) who convert to CDMS between groups | 12 months |
| New T2 brain lesions on MRI | Mean number of new T2 lesions over study between groups |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jodie Burton, MD, MSc | University of Calgary | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Foothills Medical Centre, University of Calgary | Calgary | Alberta | T2N 2T9 | Canada |
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| ID | Term |
|---|---|
| D009902 | Optic Neuritis |
| ID | Term |
|---|---|
| D009901 | Optic Nerve Diseases |
| D003389 | Cranial Nerve Diseases |
| D009422 | Nervous System Diseases |
| D005128 | Eye Diseases |
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| ID | Term |
|---|---|
| D002762 | Cholecalciferol |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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A double-blind randomized placebo/standard therapy phase II trial
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Masked randomization and allocation, only data safety monitor will know allocation if adverse event requires unblinding
| Placebo/Standard of Care Vitamin D3 | Drug | 50,000 IU/d of oral vitamin D3 x 5 days followed by 40,000 IU/d of oral vitamin D3 x 85 days |
|
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Rate of change in mean GCL thickness in affected eye over study by 25(OH)D level
| baseline to 12 months |
| Change in mean GCL IED between eyes over time | Rate of change in mean GCL IED thickness in affected eye over study between groups | baseline to 12 months |
| Change in mean GCL IED between eyes over time | Rate of change in mean GCL IED thickness in affected eye over study by 25(OH)D level | baseline to 12 months |
| Change in mean retinal nerve fiber layer (RNFL) in affected eye over time | Rate of change in mean RNFL thickness in affected eye over study between groups | baseline to 12 months |
| Change in mean RNFL in affected eye over time | Rate of change in mean RNFL thickness in affected eye over study by 25(OH)D level | baseline to 12 months |
| Change in mean RNFL IED between eyes over time | Rate of change in mean RNFL and GCL thickness in affected eye over study between groups | baseline to 12 months |
| Change in mean RNFL IED between eyes over time | Rate of change in mean RNFL and GCL thickness in affected eye over study by 25(OH)D level | baseline to 12 months |
| Mean RNFL thickness | Mean RNFL thickness at baseline and months between groups | baseline |
| Mean RNFL thickness | Mean RNFL thickness at month 1 between groups | 1 month |
| Mean RNFL thickness | Mean RNFL thickness at month 6 between groups | 6 months |
| Mean RNFL thickness | Mean RNFL thickness at month 12 between groups | 12 months |
| Mean GCL thickness | Mean GCL thickness at baseline between groups | baseline to 12 months |
| Mean GCL thickness | Mean GCL thickness at month 1 between groups | 1 month |
| Mean GCL thickness | Mean GCL thickness at month 6 between groups | 6 months |
| Mean GCL thickness | Mean GCL thickness at month 12 between groups | 12 months |
| Inter-eye RNFL thickness | The difference between the unaffected and affected eye RNFL thickness at baseline between treatment and placebo groups | baseline to 12 months |
| Inter-eye RNFL thickness | The difference between the unaffected and affected eye RNFL thickness at month 1 between treatment and placebo groups | 1 months |
| Inter-eye RNFL thickness | The difference between the unaffected and affected eye RNFL thickness at month 6 between treatment and placebo groups | 6 months |
| Inter-eye RNFL thickness | The difference between the unaffected and affected eye RNFL thickness at month 12 between treatment and placebo groups | 12 months |
| Inter-eye GCL thickness | The difference between the unaffected and affected eye GCL thickness at baseline between treatment and placebo groups | baseline |
| Inter-eye GCL thickness | The difference between the unaffected and affected eye GCL thickness at month 1 between treatment and placebo groups | 1 month |
| Inter-eye GCL thickness | The difference between the unaffected and affected eye GCL thickness at month 6 between treatment and placebo groups | 6 months |
| Inter-eye GCL thickness | The difference between the unaffected and affected eye RNFL thickness between treatment and placebo groups | 12 months |
| Mean macular volume (MV) | Mean MV at baseline between groups | baseline |
| Mean macular volume (MV) | Mean MV at month 1 between groups | 1 month |
| Mean macular volume (MV) | Mean MV at month 6 between groups | 6 months |
| Mean macular volume (MV) | Mean MV at month 12 between groups | 12 months |
| Mean multifocal VEP (MfVEP) latency | Mean MfVEP at month 1 between groups | 1 month |
| Mean change high and low contrast visual acuity (LogMAR) | Mean high and low contrast visual acuity (LogMAR) between groups at from baseline to month 12 | 12 months |
| 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 | 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 | 12 months |
| 12 months |
| New contrast enhancing brain lesions on MRI | Mean number of new contrast enhancing lesions over study between groups | 12 months |
| Exploratory novel MRI outcomes - diffusion tensor imaging (DTI) | Changes in optic nerve, tract and radiations DTI between groups over study | 12 months |
| Exploratory novel MRI outcomes - texture | Changes in optic nerve, tract and radiations texture between groups over study | 12 months |
| Exploratory novel MRI outcomes - cross-sectional area | Changes in optic nerve, tract and radiations cross-sectional area between groups over study | 12 months |
| Thalamic volume on MRI | Mean thalamic volume over study between groups | 12 months |
| D011083 |
| Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |