Immunomodulation 2Saturday, October 13, 2007, 15:30 - 17:00
A phase I dose-escalation trial of vitamin D3 with calcium supplementation in patients with multiple sclerosisJ.M. Burton, S. Kimball, R. Vieth, A. Bar-Or, H.M. Dosch, L. Thibault, S. Kilborn, C. D'Souza, M. Ursell, P. O'Connor (Toronto, Montreal, CAN)
Background: There is good evidence for a relationship between vitamin D nutritional status and development of multiple sclerosis (MS), which could explain the geographic pattern of MS prevalence. A potential mechanism is Vitamin D3ís regulatory effects on the immune system. The evidence suggests Vitamin D3 may benefit MS patients, but first, a safe and effective dose must be determined.
Objective: To characterize the safety profile of high-dose oral vitamin D3 in MS, we conducted a phase I dose-escalation trial with calcium supplementation in MS patients.
Design: In a prospective controlled 52-week trial, patients with clinically definite MS were matched for age, gender, disease duration, Expanded Disability Status Scale (EDSS) score, Disease Modifying Drugs, and MS subtype, and randomized to treatment or control groups. Treatment group patients received escalating doses of Vitamin D3 starting at 4,000 IU/d and escalating over 28 weeks to 40,000 IU/d, spending approximately 6 weeks at each dose. Patients were then maintained on 10,000 IU/d for 12 weeks, followed by a down-titration to 4,000 IU/d for 8 weeks, and a final 4-week washout period. Calcium (1200mg/d) was given orally throughout the trial. Twenty-five treatment patients and 24 matched controls were enrolled. The primary endpoint is change in serum calcium concentration in the treatment group over the 52-week period. Secondary endpoints are change over the trial in serum 25-hydroxyvitamin D (25(OH)D), parathyroid hormone, urine calcium:creatinine ratio, liver enzymes and creatinine/urea. Baseline and end-of-trial EDSS, Ambulation Index and relapse rate will be measured in all patients. Serum cytokines, lymphocyte responses and matrix metalloproteinases will be compared over the Vitamin D3 escalation in treatment patients and between treatment and control groups.
Results: At 9 months, 17/25 treatment patients have received 6 weeks of 40,000 IU/d of Vitamin D3 and are now in the 10,000 IU/d maintenance phase. There is no significant difference between groups in age, disease duration, relapse rate, prior Vitamin D3 dose, baseline serum calcium or 25(OH)D. Serum calcium has remained in the reference range (2.2-2.6mmol/L), with no significant differences over escalating doses. Mean 25(OH)D increased from 73.5 +/- 26.4mmo/L at baseline to 402.1 +/- 123.0 mmol/L at 40,000 IU/d (p<0.001).
Conclusions: The results thus far suggest high-dose Vitamin D is safe and tolerable in MS patients.