Safety Trial of High Dose Oral Vitamin D3 With Calcium in Multiple Sclerosis (VitD4MS)

• ClinicalTrials.gov Identifier: NCT00644904
• Recruitment Status: Completed
• First Posted: March 27, 2008
• Last Update Posted: March 28, 2008
• Sponsor: University of Toronto
• Collaborators: Direct MS-Proactive Charity; Multiple Sclerosis Society of Canada
• Information provided by: University of Toronto

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis	Dietary Supplement: Vitamin D3	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Dose-Escalation Trial of Vitamin D3 With Calcium Supplementation in Patients With Multiple Sclerosis
• Study Start Date: July 2006
• Actual Primary Completion Date: February 2008
• Actual Study Completion Date: February 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Dietary Supplement: Vitamin D3
Control; Patients are allowed to supplement with up to 4,000 IU per day of Vitamin D3 if desired.	Dietary Supplement: Vitamin D3

Outcome Measures

Primary Outcome Measures :

1. Serum calcium [ Time Frame: at each dose change ]

Secondary Outcome Measures :

1. Serum 25(OH)D [ Time Frame: at each dose change ]
2. EDSS [ Time Frame: at screening vs. end of trial ]
3. N-telopeptide (bone marker)
4. ALP/AST/ALT [ Time Frame: at each dose change ]
5. Creatinine/urea [ Time Frame: at each dose change ]
6. EKG [ Time Frame: at screening and end of trial ]
7. Renal ultrasound [ Time Frame: at screening, mid-trial and end of trial ]
8. Cytokine profile/MMP/lymphocyte response assay
9. Annualized relapse rate [ Time Frame: year prior to trial versus year of trial ]
10. PTH [ Time Frame: at each dose change ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

Canada, Ontario

St. Michael's Hospital

Toronto, Ontario, Canada, M5B 1W8

Sponsors and Collaborators

University of Toronto

Direct MS-Proactive Charity

Multiple Sclerosis Society of Canada

Investigators

• Principal Investigator: Jodie M Burton, MD; St. Michael's Hospital, University of Toronto
• Principal Investigator: Paul W O'Connor, MD, MSc; St. Michael's Hospital, University of Toronto

More Information

Publications:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Dr. Paul O'Connor, St. Michael's Hospital, Division of Neurology, University of Toronto
• ClinicalTrials.gov Identifier: NCT00644904
• Other Study ID Numbers: REB05-147
• First Posted: March 27, 2008
• Last Update Posted: March 28, 2008
• Last Verified: March 2008

Keywords provided by University of Toronto:

Multiple Sclerosis; Vitamin D; Safety

Additional relevant MeSH terms:

Multiple Sclerosis; Sclerosis; Vitamin D; Cholecalciferol; Vitamins; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Ergocalciferols; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents