Table 1.

Clinical trials on vitamin D for MS treatment

First author, date	Method	Participants	Intervention	Neurological/clinical measures	Neurological/clinical result
Burton, 2010 [58]	open-label randomized prospective controlled 52-week trial	MS patients 18–55 years mean EDSS: 1.34 Treatment group/control (n): 24/23	-Treatment: Increasing vitamin D3 dose up to 40,000 IU/d for 28 weeks, followed by 10,000 IU/d for 12 weeks, downtitrated to 0 IU/day plus 1200 mg calcium/d throughout the study -Control: = < 4000 IU vitamin D3/day and calcium if needed	EDSS, serum calcium level	No significant difference in relapse rate
Kampman, 2012 [59]	Randomized double-blind controlled 96-week trial	MS patients 18–55 years EDSS ≤ 4.5 Treatment group/control (n): 35/33	-Treatment: 20,000 IU vitamin D3/week, plus 500 mg calcium/day -Control:500 mg calcium/day	annual relapse rate, MSFC, EDSS, fatigue and grip strength	No significant difference in annual relapse rate, MSFC, EDSS, fatigue and grip strength
Shaygannejad, 2012 [60]	Randomized double-blind controlled 12-month trial	RRMS 15–60 years EDSS ≤ 6 Serum 25(OH)D > 40 ng/ml; and willing to continue vitamin D supplementation Treatment group/control (n): 25/25	-Treatment: 0.25 mcg calcitriol/day increased to 0.5 mcg/d after 2 weeks -Control: placebo	Relapse rate and EDSS	No significant difference in relapse rate and EDSS
Soilu-Hänninen, 2005 [61]	Randomized double-blind controlled 1-year trial	RRMS 18–55 years EDSS ≤ 5 Treatment group/control (n):34/32	-Treatment: 20,000 IU vitamin D3/week -Control: placebo (with interferon β-1b use)	EDSS, relapse rate, timed 10 foot tandem walk test, timed 25 foot walk test, brain MRI	Significant reduction in the number of T1 enhancing lesions and EDSS in treatment group No significant reduction in relapse rate
Stein, 2011 [62]	Randomized double-blind controlled 24-months trial	RRMS >18 years Treatment group/control (n): 11/12	Treatment:6000 IU vitamin D2 twice daily +1000 IU vitaminD2 daily Control:1000 IU vitamin D2 daily + placebo	MRI, relapse rate, EDSS	No significant difference in MRI findings. Follow-up EDSS was higher following high dose D2 (after adjusting for baseline EDSS), relapse rate was significantly higher in high dose group
Ongoing trials
Clinicaltrials.gov identification number	Duration	Estimated enrollment	Intervention
NCT01198132	96 weeks	250	Treatment: 100,000 IU vitamin D3/month + 3 rebif/week Control: 3 rebif/week
NCT01490502	104 weeks	172	Treatment: 5000 IU vitamin D3/day + Copaxone Control: 600 IU vitamin D3/day + Copaxone
NCT01024777	26 weeks	40	Treatment: 10,000 IU vitamin D3/day Control: 400 IU vitamin D3/day
NCT01285401	96 weeks	358	Treatment: 6670 IU vitamin D3/day for 4 weeks, 14,007 IU vitamin D3/day for the following 92 weeks + 3 Rebif /week Control: 3 Rebif /week
NCT01440062	78 weeks	80	Treatment: 20,400 IU vitamin D3 on alternate day + Interferon ß-1b Control: 400 IU vitamin D3 on alternate day + Interferon ß-1b