High-Dose Vitamin D Induction in Optic Neuritis (VitaDON2)

A Phase II Trial of High-Dose Vitamin D Induction in Optic Neuritis (VitaDON 2)

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.

Study Overview

• Status: Terminated
• Conditions: Optic Neuritis
• Intervention / Treatment: Drug: Vitamin D3; Drug: Placebo/Standard of Care Vitamin D3

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre, University of Calgary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-Dose Vitamin D Treatment Group; 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)	Drug: Vitamin 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; Other Names: Vitamin D - CHOLECALCIFEROL
Placebo Comparator: Placebo/Standard Vitamin D3 Group; 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)	Drug: Placebo/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; Other Names: Vitamin D - CHOLECALCIFEROL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Jodie Burton, MD, MSc, University Of Calgary

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2017
• Primary Completion (Actual): May 9, 2024
• Study Completion (Actual): May 9, 2024

Study Registration Dates

• First Submitted: September 27, 2017
• First Submitted That Met QC Criteria: September 30, 2017
• First Posted (Actual): October 5, 2017

Study Record Updates

• Last Update Posted (Actual): July 24, 2024
• Last Update Submitted That Met QC Criteria: July 22, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Vitamin D; Optic Neuritis
• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Neuritis; Optic Neuritis; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: REB17-0922

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No