Clinical trial NCT03302585: High-Dose Vitamin D Induction in Optic Neuritis
Official title: A Phase II Trial of High-Dose Vitamin D Induction in Optic Neuritis (VitaDON 2)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Optic Neuritis
Keywords: Optic Neuritis
Vitamin D
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2017-10-05
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A double-blind randomized placebo/standard therapy phase II trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Inter-eye (IED) ganglion cell layer thickness (GCL)
timeFrame: month 12
measure: Proportion of patients with GCL IED <= 8 microns
timeFrame: 12 months
Secondary outcomes:
measure: Change in mean GCL in affected eye over time
timeFrame: baseline to 12 months
measure: Change in mean GCL in affected eye over time
timeFrame: baseline to 12 months
measure: Change in mean GCL IED between eyes over time
timeFrame: baseline to 12 months
measure: Change in mean GCL IED between eyes over time
timeFrame: baseline to 12 months
measure: Change in mean retinal nerve fiber layer (RNFL) in affected eye over time
timeFrame: baseline to 12 months
measure: Change in mean RNFL in affected eye over time
timeFrame: baseline to 12 months
measure: Change in mean RNFL IED between eyes over time
timeFrame: baseline to 12 months
measure: Change in mean RNFL IED between eyes over time
timeFrame: baseline to 12 months
measure: Mean RNFL thickness
timeFrame: baseline
measure: Mean RNFL thickness
timeFrame: 1 month
measure: Mean RNFL thickness
timeFrame: 6 months
measure: Mean RNFL thickness
timeFrame: 12 months
measure: Mean GCL thickness
timeFrame: baseline to 12 months
measure: Mean GCL thickness
timeFrame: 1 month
measure: Mean GCL thickness
timeFrame: 6 months
measure: Mean GCL thickness
timeFrame: 12 months
measure: Inter-eye RNFL thickness
timeFrame: baseline to 12 months
measure: Inter-eye RNFL thickness
timeFrame: 1 months
measure: Inter-eye RNFL thickness
timeFrame: 6 months
measure: Inter-eye RNFL thickness
timeFrame: 12 months
measure: Inter-eye GCL thickness
timeFrame: baseline
measure: Inter-eye GCL thickness
timeFrame: 1 month
measure: Inter-eye GCL thickness
timeFrame: 6 months
measure: Inter-eye GCL thickness
timeFrame: 12 months
measure: Mean macular volume (MV)
timeFrame: baseline
measure: Mean macular volume (MV)
timeFrame: 1 month
measure: Mean macular volume (MV)
timeFrame: 6 months
measure: Mean macular volume (MV)
timeFrame: 12 months
measure: Mean multifocal VEP (MfVEP) latency
timeFrame: 1 month
measure: Mean change high and low contrast visual acuity (LogMAR)
timeFrame: 12 months
measure: 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
timeFrame: 12 months
Other outcomes:
measure: Conversion to clinically definite MS (CDMS)
timeFrame: 12 months
measure: New T2 brain lesions on MRI
timeFrame: 12 months
measure: New contrast enhancing brain lesions on MRI
timeFrame: 12 months
measure: Exploratory novel MRI outcomes - diffusion tensor imaging (DTI)
timeFrame: 12 months
measure: Exploratory novel MRI outcomes - texture
timeFrame: 12 months
measure: Exploratory novel MRI outcomes - cross-sectional area
timeFrame: 12 months
measure: Thalamic volume on MRI
timeFrame: 12 months
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre, University of Calgary
state: Alberta
Study officials:
affiliation: University of Calgary
name: Jodie Burton, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: