High-Dose Vitamin D Induction in Optic Neuritis

Phase 2TerminatedNCT03302585

University of Calgary12 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Optic Neuritis

Interventions

Vitamin D3DRUG

50,000 IU/d of oral vitamin D3 x 5 days followed by 10,000 IU/d of oral vitamin D3 x 85 days

Placebo/Standard of Care Vitamin D3DRUG

50,000 IU/d of oral vitamin D3 x 5 days followed by 40,000 IU/d of oral vitamin D3 x 85 days

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 Years

Medical Language ↔ Plain English

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

Locations (1)

Foothills Medical Centre, University of Calgary

Calgary, Alberta, Canada

Outcomes

Primary Outcomes

Inter-eye (IED) ganglion cell layer thickness (GCL)

The difference between the unaffected and affected eye GCL thickness between treatment and placebo group

Time frame: 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

Time frame: 12 months