High-dose cholecalciferol (vitamin D) supplementation has been shown to safely and significantly delay the progression from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (MS), according to data from the D-Lay-MS Phase 3 clinical trial presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual meeting. The study, led by Eric Thouvenot, MD, PhD, from the University Hospital of Nîmes, France, found that a high dose of 100,000 IU of cholecalciferol taken every other week nearly doubled the time it took for CIS patients to experience new disease activity.
The D-Lay-MS study (NCT01817166) was a 24-month placebo-controlled randomized trial designed to assess the safety and efficacy of high-dose cholecalciferol in delaying the conversion from CIS to MS. MS is characterized by the immune system attacking the myelin sheath, the protective coating around nerve cells. Low vitamin D levels have been implicated as a potential risk factor for MS development and increased disability.
Impact on Disease Activity and Lesions
The trial involved 303 adults with a median age of 34 who had experienced a CIS episode within the previous 90 days. The majority (70%) were women, and all participants had low vitamin D levels. Participants were randomly assigned to receive either 100,000 IU of cholecalciferol or a placebo every other week for up to two years. The primary endpoint was the proportion of patients with evidence of disease activity, defined as a relapse, the development of new or enlarging lesions, or the presence of an active inflammatory lesion on MRI scans.
Results indicated a significant 34% reduction in the proportion of patients with evidence of disease activity at two years in the cholecalciferol group compared to the placebo group (60.3% vs. 74.1%). The median time to experiencing disease activity was also nearly twice as long for patients taking high-dose cholecalciferol (432 vs. 224 days).
Further analysis revealed that cholecalciferol led to significant reductions in new or enlarging lesions and in inflammatory lesions after two years. However, no significant differences were observed in relapse rates, disability measures, cognition, quality of life, fatigue, anxiety, or depression.
Patient Subgroup Analysis
Subgroup analysis identified that patients who benefited the most from cholecalciferol supplementation were those without spinal cord lesions, with severe vitamin D deficiency, and with a normal body mass index at the start of the study. These findings remained consistent even after adjusting for factors such as age, sex, and the number of lesions seen on MRI scans at baseline.
Safety and Tolerability
High-dose cholecalciferol was found to be safe and well-tolerated, with 95.1% of patients completing the study. While 33 serious side effects were reported in 30 patients, none were attributed to cholecalciferol supplementation.
"In line with previous studies, high-dose vitamin D supplementation was safe and well tolerated," Thouvenot said. "Together with the excellent safety profile, these data support high-dose vitamin D supplementation in early MS and make vitamin D the best candidate for add-on therapy evaluation in the therapeutic strategy for MS."
