CClinicalTrials.gg
Sign In
TerminatedNCT03302585VitaDON2Updated Jul 24, 2024

High-Dose Vitamin D Induction in Optic Neuritis

A Phase 2 interventional study of Vitamin D3 and Placebo/Standard of Care Vitamin D3 in Optic Neuritis, sponsored by University of Calgary. Terminated at 1 site in Canada. Open to participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2024-07-24.

Sponsored by University of Calgary · Phase 2, Interventional, and Treatment

Why this study was terminated
inability to meet recruitment goals
Phase
Phase 2
Study type
Interventional
Enrollment
12
Allocation
Randomized
Ages
18 Years to 45 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Optic Neuritis

Keywords

  • Optic Neuritis
  • Vitamin D
03

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
12 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • DrugVitamin 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

    Also known as: Vitamin D - CHOLECALCIFEROL

  • DrugPlacebo/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

    Also known as: Vitamin D - CHOLECALCIFEROL

05

What researchers measure

Primary outcomes

  1. 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

  2. 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

Secondary outcomes

  1. Change in mean GCL in affected eye over time

    Rate of change in mean GCL thickness in affected eye over study between groups

    Time frame: baseline to 12 months

  2. 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

    Time frame: baseline to 12 months

  3. Change in mean GCL IED between eyes over time

    Rate of change in mean GCL IED thickness in affected eye over study between groups

    Time frame: baseline to 12 months

  4. 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

    Time frame: baseline to 12 months

  5. 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

    Time frame: baseline to 12 months

  6. 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

    Time frame: baseline to 12 months

  7. 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

    Time frame: baseline to 12 months

  8. 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

    Time frame: baseline to 12 months

  9. Mean RNFL thickness

    Mean RNFL thickness at baseline and months between groups

    Time frame: baseline

  10. Mean RNFL thickness

    Mean RNFL thickness at month 1 between groups

    Time frame: 1 month

  11. Mean RNFL thickness

    Mean RNFL thickness at month 6 between groups

    Time frame: 6 months

  12. Mean RNFL thickness

    Mean RNFL thickness at month 12 between groups

    Time frame: 12 months

  13. Mean GCL thickness

    Mean GCL thickness at baseline between groups

    Time frame: baseline to 12 months

  14. Mean GCL thickness

    Mean GCL thickness at month 1 between groups

    Time frame: 1 month

  15. Mean GCL thickness

    Mean GCL thickness at month 6 between groups

    Time frame: 6 months

  16. Mean GCL thickness

    Mean GCL thickness at month 12 between groups

    Time frame: 12 months

  17. Inter-eye RNFL thickness

    The difference between the unaffected and affected eye RNFL thickness at baseline between treatment and placebo groups

    Time frame: baseline to 12 months

  18. Inter-eye RNFL thickness

    The difference between the unaffected and affected eye RNFL thickness at month 1 between treatment and placebo groups

    Time frame: 1 months

  19. Inter-eye RNFL thickness

    The difference between the unaffected and affected eye RNFL thickness at month 6 between treatment and placebo groups

    Time frame: 6 months

  20. Inter-eye RNFL thickness

    The difference between the unaffected and affected eye RNFL thickness at month 12 between treatment and placebo groups

    Time frame: 12 months

  21. Inter-eye GCL thickness

    The difference between the unaffected and affected eye GCL thickness at baseline between treatment and placebo groups

    Time frame: baseline

  22. Inter-eye GCL thickness

    The difference between the unaffected and affected eye GCL thickness at month 1 between treatment and placebo groups

    Time frame: 1 month

  23. Inter-eye GCL thickness

    The difference between the unaffected and affected eye GCL thickness at month 6 between treatment and placebo groups

    Time frame: 6 months

  24. Inter-eye GCL thickness

    The difference between the unaffected and affected eye RNFL thickness between treatment and placebo groups

    Time frame: 12 months

  25. Mean macular volume (MV)

    Mean MV at baseline between groups

    Time frame: baseline

  26. Mean macular volume (MV)

    Mean MV at month 1 between groups

    Time frame: 1 month

  27. Mean macular volume (MV)

    Mean MV at month 6 between groups

    Time frame: 6 months

  28. Mean macular volume (MV)

    Mean MV at month 12 between groups

    Time frame: 12 months

  29. Mean multifocal VEP (MfVEP) latency

    Mean MfVEP at month 1 between groups

    Time frame: 1 month

  30. 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

    Time frame: 12 months

  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

    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 outcomes

  1. Conversion to clinically definite MS (CDMS)

    Proportion of patients with clinically isolated syndromes (CIS) who convert to CDMS between groups

    Time frame: 12 months

  2. New T2 brain lesions on MRI

    Mean number of new T2 lesions over study between groups

    Time frame: 12 months

  3. New contrast enhancing brain lesions on MRI

    Mean number of new contrast enhancing lesions over study between groups

    Time frame: 12 months

  4. Exploratory novel MRI outcomes - diffusion tensor imaging (DTI)

    Changes in optic nerve, tract and radiations DTI between groups over study

    Time frame: 12 months

  5. Exploratory novel MRI outcomes - texture

    Changes in optic nerve, tract and radiations texture between groups over study

    Time frame: 12 months

  6. Exploratory novel MRI outcomes - cross-sectional area

    Changes in optic nerve, tract and radiations cross-sectional area between groups over study

    Time frame: 12 months

  7. Thalamic volume on MRI

    Mean thalamic volume over study between groups

    Time frame: 12 months

06

Study locations

1 site
  • Foothills Medical Centre, University of Calgary
    Calgary, Alberta T2N 2T9, Canada
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03302585
Lead sponsor
University of Calgary
Responsible party
Jodie Burton MD, MSc, FRCPC (Assistant Professor, University of Calgary) — Principal investigator
First posted
Oct 5, 2017
Start date
Nov 23, 2017
Primary completion
May 9, 2024
Completion
May 9, 2024
Last update
Jul 24, 2024

Study contacts

Jodie Burton, MD, MSc
principal investigator · University of Calgary

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Jul 2024. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Neuritis→

Other studies from this sponsor

University of Calgary

Start the discussion