A Phase I/II Dose-Escalation Trial of Vitamin D3 With Calcium Supplementation in Patients With Multiple Sclerosis
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- University of Toronto
- Enrollment
- 49
- Locations
- 1
- Primary Endpoint
- Serum calcium
Study Overview
Brief Summary
Vitamin D likely plays a role in the geography of Multiple Sclerosis (MS), and patients at risk and with MS have relatively low Vitamin D levels compared to their normal counterparts.
This trial examines the safety of high dose oral Vitamin D3 titrated up to a maximum of 40,000 IU per day over a 12 month period. Fifty patients matched for MS and non-MS characteristics will be divided into two groups: one group receiving the high dose Vitamin D regimen, and the other restricted to a maximum of 4000 IU per day. The hypothesis is that patients with MS can tolerate seemingly high doses of Vitamin D3 without adverse events and/or calcium-related abnormalities. It is also hypothesized that those receiving the higher doses will demonstrate improved relapse and disability status compared to controls, and that the treatment group will show improved markers of bone health and immune indicators of reduced inflammation.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Clinically definite MS
- •Age 18-55
- •EDSS 0-6.5
Exclusion Criteria
- •EDSS => 7.0
- •Current Vitamin D3 use >4000 IU/d
- •Baseline (25(OH)D) level <20 mmol/L (frank deficiency) and >150 mmol/L
- •Pregnancy or inability/unwillingness to use contraception
- •History of cardiac arrhythmia
- •History of renal disease and nephrolithiasis
- •History of granulomatous disease or lymphoma
- •Relapse activity or steroid use in the past 60 days
Arms & Interventions
Control
Patients are allowed to supplement with up to 4,000 IU per day of Vitamin D3 if desired.
Intervention: Vitamin D3 (Dietary Supplement)
Treatment
Starting dose of 4,000 IU per day of Vitamin D3 titrating up to a dose of 40,000 IU per day of Vitamin D3 by month six. In the second six-month part of the trial, patients titrate back down to 4,000 IU per day of Vitamin D3 and then discontinue it completely at the end of the 12 month trial period.
Intervention: Vitamin D3 (Dietary Supplement)
Outcomes
Primary Outcomes
Serum calcium
Time Frame: at each dose change
Secondary Outcomes
- Serum 25(OH)D(at each dose change)
- EDSS(at screening vs. end of trial)
- N-telopeptide (bone marker)
- ALP/AST/ALT(at each dose change)
- Creatinine/urea(at each dose change)
- EKG(at screening and end of trial)
- Renal ultrasound(at screening, mid-trial and end of trial)
- Cytokine profile/MMP/lymphocyte response assay
- Annualized relapse rate(year prior to trial versus year of trial)
- PTH(at each dose change)