search
Back to results

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

Primary Purpose

Optic Neuritis

Status
Unknown status
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Vitamin D3
Placebo/Standard of Care Vitamin D3
Sponsored by
University of Calgary
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Optic Neuritis focused on measuring Optic Neuritis, Vitamin D

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Foothills Medical Centre, University of CalgaryRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

High-Dose Vitamin D Treatment Group

Placebo/Standard Vitamin D3 Group

Arm Description

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)

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)

Outcomes

Primary Outcome Measures

Inter-eye (IED) ganglion cell layer thickness (GCL)
The difference between the unaffected and affected eye GCL thickness between treatment and placebo group
Proportion of patients with GCL IED <= 8 microns
The proportion of patients with unaffected and affected eye GCL thickness of < = 8 microns between groups

Secondary Outcome Measures

Change in mean GCL in affected eye over time
Rate of change in mean GCL thickness in affected eye over study between groups
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
Change in mean GCL IED between eyes over time
Rate of change in mean GCL IED thickness in affected eye over study between groups
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
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
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
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
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
Mean RNFL thickness
Mean RNFL thickness at baseline and months between groups
Mean RNFL thickness
Mean RNFL thickness at month 1 between groups
Mean RNFL thickness
Mean RNFL thickness at month 6 between groups
Mean RNFL thickness
Mean RNFL thickness at month 12 between groups
Mean GCL thickness
Mean GCL thickness at baseline between groups
Mean GCL thickness
Mean GCL thickness at month 1 between groups
Mean GCL thickness
Mean GCL thickness at month 6 between groups
Mean GCL thickness
Mean GCL thickness at month 12 between groups
Inter-eye RNFL thickness
The difference between the unaffected and affected eye RNFL thickness at baseline between treatment and placebo groups
Inter-eye RNFL thickness
The difference between the unaffected and affected eye RNFL thickness at month 1 between treatment and placebo groups
Inter-eye RNFL thickness
The difference between the unaffected and affected eye RNFL thickness at month 6 between treatment and placebo groups
Inter-eye RNFL thickness
The difference between the unaffected and affected eye RNFL thickness at month 12 between treatment and placebo groups
Inter-eye GCL thickness
The difference between the unaffected and affected eye GCL thickness at baseline between treatment and placebo groups
Inter-eye GCL thickness
The difference between the unaffected and affected eye GCL thickness at month 1 between treatment and placebo groups
Inter-eye GCL thickness
The difference between the unaffected and affected eye GCL thickness at month 6 between treatment and placebo groups
Inter-eye GCL thickness
The difference between the unaffected and affected eye RNFL thickness between treatment and placebo groups
Mean macular volume (MV)
Mean MV at baseline between groups
Mean macular volume (MV)
Mean MV at month 1 between groups
Mean macular volume (MV)
Mean MV at month 6 between groups
Mean macular volume (MV)
Mean MV at month 12 between groups
Mean multifocal VEP (MfVEP) latency
Mean MfVEP at month 1 between groups
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
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

Full Information

First Posted
September 27, 2017
Last Updated
February 5, 2019
Sponsor
University of Calgary
search

1. Study Identification

Unique Protocol Identification Number
NCT03302585
Brief Title
High-Dose Vitamin D Induction in Optic Neuritis
Acronym
VitaDON2
Official Title
A Phase II Trial of High-Dose Vitamin D Induction in Optic Neuritis (VitaDON 2)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Unknown status
Study Start Date
November 23, 2017 (Actual)
Primary Completion Date
November 2022 (Anticipated)
Study Completion Date
April 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Calgary

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Optic Neuritis
Keywords
Optic Neuritis, Vitamin D

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
A double-blind randomized placebo/standard therapy phase II trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Masked randomization and allocation, only data safety monitor will know allocation if adverse event requires unblinding
Allocation
Randomized
Enrollment
66 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
High-Dose Vitamin D Treatment Group
Arm Type
Experimental
Arm Description
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)
Arm Title
Placebo/Standard Vitamin D3 Group
Arm Type
Placebo Comparator
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Vitamin D3
Other Intervention Name(s)
Vitamin D - CHOLECALCIFEROL
Intervention Description
50,000 IU/d of oral vitamin D3 x 5 days followed by 10,000 IU/d of oral vitamin D3 x 85 days
Intervention Type
Drug
Intervention Name(s)
Placebo/Standard of Care Vitamin D3
Other Intervention Name(s)
Vitamin D - CHOLECALCIFEROL
Intervention Description
50,000 IU/d of oral vitamin D3 x 5 days followed by 40,000 IU/d of oral vitamin D3 x 85 days
Primary Outcome Measure Information:
Title
Inter-eye (IED) ganglion cell layer thickness (GCL)
Description
The difference between the unaffected and affected eye GCL thickness between treatment and placebo group
Time Frame
month 12
Title
Proportion of patients with GCL IED <= 8 microns
Description
The proportion of patients with unaffected and affected eye GCL thickness of < = 8 microns between groups
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Change in mean GCL in affected eye over time
Description
Rate of change in mean GCL thickness in affected eye over study between groups
Time Frame
baseline to 12 months
Title
Change in mean GCL in affected eye over time
Description
Rate of change in mean GCL thickness in affected eye over study by 25(OH)D level
Time Frame
baseline to 12 months
Title
Change in mean GCL IED between eyes over time
Description
Rate of change in mean GCL IED thickness in affected eye over study between groups
Time Frame
baseline to 12 months
Title
Change in mean GCL IED between eyes over time
Description
Rate of change in mean GCL IED thickness in affected eye over study by 25(OH)D level
Time Frame
baseline to 12 months
Title
Change in mean retinal nerve fiber layer (RNFL) in affected eye over time
Description
Rate of change in mean RNFL thickness in affected eye over study between groups
Time Frame
baseline to 12 months
Title
Change in mean RNFL in affected eye over time
Description
Rate of change in mean RNFL thickness in affected eye over study by 25(OH)D level
Time Frame
baseline to 12 months
Title
Change in mean RNFL IED between eyes over time
Description
Rate of change in mean RNFL and GCL thickness in affected eye over study between groups
Time Frame
baseline to 12 months
Title
Change in mean RNFL IED between eyes over time
Description
Rate of change in mean RNFL and GCL thickness in affected eye over study by 25(OH)D level
Time Frame
baseline to 12 months
Title
Mean RNFL thickness
Description
Mean RNFL thickness at baseline and months between groups
Time Frame
baseline
Title
Mean RNFL thickness
Description
Mean RNFL thickness at month 1 between groups
Time Frame
1 month
Title
Mean RNFL thickness
Description
Mean RNFL thickness at month 6 between groups
Time Frame
6 months
Title
Mean RNFL thickness
Description
Mean RNFL thickness at month 12 between groups
Time Frame
12 months
Title
Mean GCL thickness
Description
Mean GCL thickness at baseline between groups
Time Frame
baseline to 12 months
Title
Mean GCL thickness
Description
Mean GCL thickness at month 1 between groups
Time Frame
1 month
Title
Mean GCL thickness
Description
Mean GCL thickness at month 6 between groups
Time Frame
6 months
Title
Mean GCL thickness
Description
Mean GCL thickness at month 12 between groups
Time Frame
12 months
Title
Inter-eye RNFL thickness
Description
The difference between the unaffected and affected eye RNFL thickness at baseline between treatment and placebo groups
Time Frame
baseline to 12 months
Title
Inter-eye RNFL thickness
Description
The difference between the unaffected and affected eye RNFL thickness at month 1 between treatment and placebo groups
Time Frame
1 months
Title
Inter-eye RNFL thickness
Description
The difference between the unaffected and affected eye RNFL thickness at month 6 between treatment and placebo groups
Time Frame
6 months
Title
Inter-eye RNFL thickness
Description
The difference between the unaffected and affected eye RNFL thickness at month 12 between treatment and placebo groups
Time Frame
12 months
Title
Inter-eye GCL thickness
Description
The difference between the unaffected and affected eye GCL thickness at baseline between treatment and placebo groups
Time Frame
baseline
Title
Inter-eye GCL thickness
Description
The difference between the unaffected and affected eye GCL thickness at month 1 between treatment and placebo groups
Time Frame
1 month
Title
Inter-eye GCL thickness
Description
The difference between the unaffected and affected eye GCL thickness at month 6 between treatment and placebo groups
Time Frame
6 months
Title
Inter-eye GCL thickness
Description
The difference between the unaffected and affected eye RNFL thickness between treatment and placebo groups
Time Frame
12 months
Title
Mean macular volume (MV)
Description
Mean MV at baseline between groups
Time Frame
baseline
Title
Mean macular volume (MV)
Description
Mean MV at month 1 between groups
Time Frame
1 month
Title
Mean macular volume (MV)
Description
Mean MV at month 6 between groups
Time Frame
6 months
Title
Mean macular volume (MV)
Description
Mean MV at month 12 between groups
Time Frame
12 months
Title
Mean multifocal VEP (MfVEP) latency
Description
Mean MfVEP at month 1 between groups
Time Frame
1 month
Title
Mean change high and low contrast visual acuity (LogMAR)
Description
Mean high and low contrast visual acuity (LogMAR) between groups at from baseline to month 12
Time Frame
12 months
Title
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
Description
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
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
Conversion to clinically definite MS (CDMS)
Description
Proportion of patients with clinically isolated syndromes (CIS) who convert to CDMS between groups
Time Frame
12 months
Title
New T2 brain lesions on MRI
Description
Mean number of new T2 lesions over study between groups
Time Frame
12 months
Title
New contrast enhancing brain lesions on MRI
Description
Mean number of new contrast enhancing lesions over study between groups
Time Frame
12 months
Title
Exploratory novel MRI outcomes - diffusion tensor imaging (DTI)
Description
Changes in optic nerve, tract and radiations DTI between groups over study
Time Frame
12 months
Title
Exploratory novel MRI outcomes - texture
Description
Changes in optic nerve, tract and radiations texture between groups over study
Time Frame
12 months
Title
Exploratory novel MRI outcomes - cross-sectional area
Description
Changes in optic nerve, tract and radiations cross-sectional area between groups over study
Time Frame
12 months
Title
Thalamic volume on MRI
Description
Mean thalamic volume over study between groups
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Martha Rojas Zavala
Phone
403 944-4244
Email
Martha.RojasZavala@albertahealthservices.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jodie Burton, MD, MSc
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
Facility Information:
Facility Name
Foothills Medical Centre, University of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 2T9
Country
Canada
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

High-Dose Vitamin D Induction in Optic Neuritis

We'll reach out to this number within 24 hrs