Clinical trial NCT00644904: Safety Trial of High Dose Oral Vitamin D3 With Calcium in Multiple Sclerosis
Official title: A Phase I/II Dose-Escalation Trial of Vitamin D3 With Calcium Supplementation in Patients With Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Vitamin D
Safety
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: Direct MS-Proactive Charity
name: Multiple Sclerosis Society of Canada
First posted: 2008-03-27
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Serum calcium
timeFrame: at each dose change
Secondary outcomes:
measure: Serum 25(OH)D
timeFrame: at each dose change
measure: EDSS
timeFrame: at screening vs. end of trial
measure: N-telopeptide (bone marker)
measure: ALP/AST/ALT
timeFrame: at each dose change
measure: Creatinine/urea
timeFrame: at each dose change
measure: EKG
timeFrame: at screening and end of trial
measure: Renal ultrasound
timeFrame: at screening, mid-trial and end of trial
measure: Cytokine profile/MMP/lymphocyte response assay
measure: Annualized relapse rate
timeFrame: year prior to trial versus year of trial
measure: PTH
timeFrame: at each dose change
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
Study officials:
affiliation: St. Michael's Hospital, University of Toronto
name: Jodie M Burton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Michael's Hospital, University of Toronto
name: Paul W O'Connor, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kimball SM, Ursell MR, O'Connor P, Vieth R. Safety of vitamin D3 in adults with multiple sclerosis. Am J Clin Nutr. 2007 Sep;86(3):645-51. doi: 10.1093/ajcn/86.3.645.
citation: Kimball S, Vieth R, Dosch HM, Bar-Or A, Cheung R, Gagne D, O'Connor P, D'Souza C, Ursell M, Burton JM. Cholecalciferol plus calcium suppresses abnormal PBMC reactivity in patients with multiple sclerosis. J Clin Endocrinol Metab. 2011 Sep;96(9):2826-34. doi: 10.1210/jc.2011-0325. Epub 2011 Jun 22.
citation: Kimball SM, Burton JM, O'Connor PG, Vieth R. Urinary calcium response to high dose vitamin D3 with calcium supplementation in patients with multiple sclerosis. Clin Biochem. 2011 Jul;44(10-11):930-2. doi: 10.1016/j.clinbiochem.2011.04.017. Epub 2011 May 5.