Efficacy of Vitamin D Supplementation in Multiple Sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial

Abstract

BackgroundMultiple sclerosis is the most common chronic inflammatory disease of the central nervous system in young adults. Despite the fact that numerous lines of evidence link both the risk of disease development and the disease course to the serum level of 25-hydroxyvitamin D it still remains elusive whether multiple sclerosis patients benefit from boosting the serum level of 25-hydroxyvitamin D, mainly because interventional clinical trials that directly address the therapeutic effects of vitamin D in multiple sclerosis are sparse. We here present the protocol of an interventional clinical phase II study to test the hypothesis, that high-dose vitamin D supplementation of multiple sclerosis patients is safe and superior to low-dose supplementation with respect to beneficial therapeutic effects.Methods/DesignThe EVIDIMS trial is a German multi-center, stratified, randomized, controlled and double-blind clinical phase II pilot study. Eighty patients with the diagnosis of definite multiple sclerosis or clinically isolated syndrome who are on a stable immunomodulatory treatment with interferon-β1b will be randomized to additionally receive either high-dose (average daily dose 10.200 IU) or low-dose (average daily dose 200 IU) cholecalciferol for a total period of 18 months. The primary outcome measure is the number of new lesions detected on T2-weighted cranial MRI at 3 tesla. Secondary endpoints include additional magnetic resonance imaging and optical coherence tomography parameters for neuroinflammation and -degeneration, clinical parameters for disease activity, as well as cognition, fatigue, depression, and quality of life. Safety and tolerability of high-dose vitamin D supplementation are further outcome parameters.DiscussionIn light of the discrepancy between existing epidemiological and preclinical data on the one hand and available clinical data on the other the EVIDIMS trial will substantially contribute to the evaluation of the efficacy of high-dose vitamin D supplementation in MS patients. The study design presented here fulfills the criteria of a high-quality clinical phase II trial in MS.Trial RegistrationClinicalTrials.gov Identifier: NCT01440062

Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis

“…Randomized controlled trials are currently underway to examine the effects of vitamin D supplementation on clinical and radiologic outcomes, with dosages of 5,000 to 10,000 IU daily. [23][24][25] …”

The effect of high dose of Vitamin D3 on the prognosis of patients with Multiple Sclerosis

“…A reduction of 1.5 new lesions in high-dose treatment is expected. The authors point out that the vitamin is safe, the treatment is cheap and that this study can fill the gaps that still exist regarding the immunomodulatory effects on Multiple Sclerosis [11].…”

“…Studies and sample protocols of that review showed that the reduction of injuries is expected in the intervention group with high dose of vitamin D3 [11], calcium levels remained normal, and there were no adverse effects [12][13][14][15][16][17][18][19]. It demonstrated that treatment with high dose of vitamin D3 lowers the proportion of IFN-ɣ and TCD4 +IL-17 and is safe.…”

The role of epidemiology in MS research: Past successes, current challenges and future potential

“…[25][26][27][28] These trials, while mostly of sufficient dosages and duration to assess treatment efficacy, are quite small in sample size. Thus, we are anxiously awaiting the results of the larger trials, including SOLAR, 29 EVIDIMS 30 and PREVANZ. 31 The story of vitamin D/UVR and MS provides a nice example of how research evolves from the observations of patterns in data, leading to hypotheses as to mechanisms, and ultimately, leading to a consensus that factors are truly causally related to a disease or disease progression.…”