The D-Lay MS randomized clinical trial, conducted at 36 multiple sclerosis centers in France, evaluated the efficacy of high-dose oral cholecalciferol (100 000 IU) administered every two weeks in patients with clinically isolated syndrome typical for multiple sclerosis.

Among 303 treated participants, disease activity—defined as clinical relapse or magnetic resonance imaging (MRI) activity—was observed in 60.3% of the vitamin D group and 74.1% of the placebo group (hazard ratio [HR], 0.66 [95% CI, 0.50-0.87]; P = .004). Median time to disease activity was 432 days in the vitamin D group compared with 224 days in the placebo group. All secondary MRI outcomes showed statistically significant differences favoring vitamin D treatment: MRI activity (57.1% vs 65.3%; HR, 0.71 [95% CI, 0.53-0.95]; P = .02), new lesions (46.2% vs 59.2%; HR, 0.61 [95% CI, 0.44-0.84]; P = .003), and contrast-enhancing lesions (18.6% vs 34.0%; HR, 0.47 [95% CI, 0.30-0.75]; P = .001).

The study included a treatment group with a median age of 34 years (interquartile range [IQR], 28-42 years), with 70% female participants. Inclusion criteria required serum vitamin D concentration less than 100 nmol/L at baseline, and severe vitamin D deficiency (<30 nmol/L) was present in 22.4% of participants. Randomization occurred within 90 days of clinically isolated syndrome (CIS) onset. The number needed to treat (NNT) to prevent one case of disease activity over 24 months was 7.2. Serious adverse events were comparable between groups and were not attributed to the study drug. No cases of moderate or severe hypercalcemia were reported.

In a subgroup of 247 participants who met the 2017 McDonald diagnostic criteria for relapsing-remitting multiple sclerosis (MS) at baseline, results were consistent with the primary analysis. The benefit was greatest among participants without spinal cord lesions at diagnosis, those with severe vitamin D deficiency, and those with a body mass index less than 25.

Vitamin D supplementation did not significantly affect other secondary clinical outcomes, including Expanded Disability Status Scale (EDSS) scores, cognitive performance, fatigue, mood, or quality-of-life measures.

The investigators concluded: "This randomized clinical trial showed the efficacy and low risk of adverse events of oral cholecalciferol 100 000 IU monotherapy every two weeks to reduce disease activity in patients with CIS and early relapsing-remitting MS. These results make high-dose vitamin D an interesting candidate for further studies evaluating add-on therapy in the therapeutic strategy for managing MS."

The trial enrolled participants between July 2013 and December 2020, with final follow-up in January 2023. Randomization was stratified by center and baseline MRI findings. The study was supported by Programme Hospitalier de Recherche Clinique (PHRC) from the French Ministry of Health. The trial was registered at ClinicalTrials.gov (NCT01817166).

Full disclosure of funding and conflicts of interest is available in the published article.

Source: JAMA