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

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ClinicalTrials.gov Identifier: NCT03302585
Recruitment Status : Recruiting
First Posted : October 5, 2017
Last Update Posted : December 4, 2017
Sponsor:
Information provided by (Responsible Party):
Jodie Burton MD, MSc, FRCPC, University of Calgary

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.

Condition or disease Intervention/treatment Phase
Optic Neuritis Drug: Vitamin D3 Drug: Placebo/Standard of Care Vitamin D3 Phase 2

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  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A double-blind randomized placebo/standard therapy phase II trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Masked randomization and allocation, only data safety monitor will know allocation if adverse event requires unblinding
Primary Purpose: Treatment
Official Title: A Phase II Trial of High-Dose Vitamin D Induction in Optic Neuritis (VitaDON 2)
Actual Study Start Date : November 23, 2017
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : April 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin D

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 Name: 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 Name: Vitamin D - CHOLECALCIFEROL




Primary Outcome Measures :
  1. Inter-eye (IED) ganglion cell layer thickness (GCL) [ Time Frame: month 12 ]
    The difference between the unaffected and affected eye GCL thickness between treatment and placebo group

  2. Proportion of patients with GCL IED <= 8 microns [ Time Frame: 12 months ]
    The proportion of patients with unaffected and affected eye GCL thickness of < = 8 microns between groups


Secondary Outcome Measures :
  1. Change in mean GCL in affected eye over time [ Time Frame: baseline to 12 months ]
    Rate of change in mean GCL thickness in affected eye over study between groups

  2. Change in mean GCL in affected eye over time [ Time Frame: baseline to 12 months ]
    Rate of change in mean GCL thickness in affected eye over study by 25(OH)D level

  3. Change in mean GCL IED between eyes over time [ Time Frame: baseline to 12 months ]
    Rate of change in mean GCL IED thickness in affected eye over study between groups

  4. Change in mean GCL IED between eyes over time [ Time Frame: baseline to 12 months ]
    Rate of change in mean GCL IED thickness in affected eye over study by 25(OH)D level

  5. Change in mean retinal nerve fiber layer (RNFL) in affected eye over time [ Time Frame: baseline to 12 months ]
    Rate of change in mean RNFL thickness in affected eye over study between groups

  6. Change in mean RNFL in affected eye over time [ Time Frame: baseline to 12 months ]
    Rate of change in mean RNFL thickness in affected eye over study by 25(OH)D level

  7. Change in mean RNFL IED between eyes over time [ Time Frame: baseline to 12 months ]
    Rate of change in mean RNFL and GCL thickness in affected eye over study between groups

  8. Change in mean RNFL IED between eyes over time [ Time Frame: baseline to 12 months ]
    Rate of change in mean RNFL and GCL thickness in affected eye over study by 25(OH)D level

  9. Mean RNFL thickness [ Time Frame: baseline ]
    Mean RNFL thickness at baseline and months between groups

  10. Mean RNFL thickness [ Time Frame: 1 month ]
    Mean RNFL thickness at month 1 between groups

  11. Mean RNFL thickness [ Time Frame: 6 months ]
    Mean RNFL thickness at month 6 between groups

  12. Mean RNFL thickness [ Time Frame: 12 months ]
    Mean RNFL thickness at month 12 between groups

  13. Mean GCL thickness [ Time Frame: baseline to 12 months ]
    Mean GCL thickness at baseline between groups

  14. Mean GCL thickness [ Time Frame: 1 month ]
    Mean GCL thickness at month 1 between groups

  15. Mean GCL thickness [ Time Frame: 6 months ]
    Mean GCL thickness at month 6 between groups

  16. Mean GCL thickness [ Time Frame: 12 months ]
    Mean GCL thickness at month 12 between groups

  17. Inter-eye RNFL thickness [ Time Frame: baseline to 12 months ]
    The difference between the unaffected and affected eye RNFL thickness at baseline between treatment and placebo groups

  18. Inter-eye RNFL thickness [ Time Frame: 1 months ]
    The difference between the unaffected and affected eye RNFL thickness at month 1 between treatment and placebo groups

  19. Inter-eye RNFL thickness [ Time Frame: 6 months ]
    The difference between the unaffected and affected eye RNFL thickness at month 6 between treatment and placebo groups

  20. Inter-eye RNFL thickness [ Time Frame: 12 months ]
    The difference between the unaffected and affected eye RNFL thickness at month 12 between treatment and placebo groups

  21. Inter-eye GCL thickness [ Time Frame: baseline ]
    The difference between the unaffected and affected eye GCL thickness at baseline between treatment and placebo groups

  22. Inter-eye GCL thickness [ Time Frame: 1 month ]
    The difference between the unaffected and affected eye GCL thickness at month 1 between treatment and placebo groups

  23. Inter-eye GCL thickness [ Time Frame: 6 months ]
    The difference between the unaffected and affected eye GCL thickness at month 6 between treatment and placebo groups

  24. Inter-eye GCL thickness [ Time Frame: 12 months ]
    The difference between the unaffected and affected eye RNFL thickness between treatment and placebo groups

  25. Mean macular volume (MV) [ Time Frame: baseline ]
    Mean MV at baseline between groups

  26. Mean macular volume (MV) [ Time Frame: 1 month ]
    Mean MV at month 1 between groups

  27. Mean macular volume (MV) [ Time Frame: 6 months ]
    Mean MV at month 6 between groups

  28. Mean macular volume (MV) [ Time Frame: 12 months ]
    Mean MV at month 12 between groups

  29. Mean multifocal VEP (MfVEP) latency [ Time Frame: 1 month ]
    Mean MfVEP at month 1 between groups

  30. Mean change high and low contrast visual acuity (LogMAR) [ Time Frame: 12 months ]
    Mean high and low contrast visual acuity (LogMAR) between groups at from baseline to month 12

  31. 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 [ Time Frame: 12 months ]
    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


Other Outcome Measures:
  1. Conversion to clinically definite MS (CDMS) [ Time Frame: 12 months ]
    Proportion of patients with clinically isolated syndromes (CIS) who convert to CDMS between groups

  2. New T2 brain lesions on MRI [ Time Frame: 12 months ]
    Mean number of new T2 lesions over study between groups

  3. New contrast enhancing brain lesions on MRI [ Time Frame: 12 months ]
    Mean number of new contrast enhancing lesions over study between groups

  4. Exploratory novel MRI outcomes - diffusion tensor imaging (DTI) [ Time Frame: 12 months ]
    Changes in optic nerve, tract and radiations DTI between groups over study

  5. Exploratory novel MRI outcomes - texture [ Time Frame: 12 months ]
    Changes in optic nerve, tract and radiations texture between groups over study

  6. Exploratory novel MRI outcomes - cross-sectional area [ Time Frame: 12 months ]
    Changes in optic nerve, tract and radiations cross-sectional area between groups over study

  7. Thalamic volume on MRI [ Time Frame: 12 months ]
    Mean thalamic volume over study between groups



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03302585


Contacts
Contact: Rand Pasha 403 944-4244 rand.pasha@ahs.ca

Locations
Canada, Alberta
Foothills Medical Centre, University of Calgary Recruiting
Calgary, Alberta, Canada, T2N 2T9
Sponsors and Collaborators
University of Calgary
Investigators
Principal Investigator: Jodie Burton, MD, MSc, FRCPC University of Calgary

Responsible Party: Jodie Burton MD, MSc, FRCPC, Assistant Professor, University of Calgary
ClinicalTrials.gov Identifier: NCT03302585     History of Changes
Other Study ID Numbers: REB17-0922
First Posted: October 5, 2017    Key Record Dates
Last Update Posted: December 4, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jodie Burton MD, MSc, FRCPC, University of Calgary:
Optic Neuritis
Vitamin D

Additional relevant MeSH terms:
Vitamins
Vitamin D
Neuritis
Optic Neuritis
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Optic Nerve Diseases
Cranial Nerve Diseases
Eye Diseases
Ergocalciferols
Cholecalciferol
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents