Effect of Alfacalcidol on multiple sclerosis-related fatigue: A randomized, double-blind placebo-controlled study

Anat Achiron*, Uri Givon, David Magalashvili, Mark Dolev, Sigal Liraz Zaltzman, Alon Kalron, Yael Stern, Zeev Mazor, David Ladkani, Yoram Barak

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Context: Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS); however, there is no medication that has been approved specifically to treat MS-related fatigue. Objective: We aimed to evaluate the effect of vitamin D analogue, Alfacalcidol, on MS-related fatigue. Design, settings, participants: This was a randomized, double-blind, parallel group, placebo-controlled trial in patients with clinically definite MS by McDonald criteria conducted in a single university-affiliated medical center in Israel. Randomly selected patients from the Sheba MS Registry computerized database (N=600) were assessed using the self-report Fatigue Severity Scale (FSS). Patients with clinically meaningful fatigue (N=259) were further assessed for trial eligibility, and MS patients with significant fatigue (N=158; 61%, 118 females, mean age 41.1 ± 9.2 years and mean disease duration of 6.2 ± 5.5 years) were included in the study and randomized to receive treatment or placebo. Intervention: Alfacalcidol (1 mcg/d, N=80) or placebo (N=78) was administered for six consecutive months. Main outcome measure: The primary endpoint of the study was the change between Alfacalcidol and placebo-treated patients in the Fatigue Impact Scale (FIS) score; the cut-off point for improvement was defined as 30% decrease. All analyses followed the intention-to-treat principle and were performed for all participants based on the group they were randomly allocated regardless of whether or not they dropped out. Results: Alfacalcidol decreased the mean relative FIS score as compared with placebo (41.6% vs. 27.4%, p=0.007, respectively). This advantage was further emphasized when the modified FIS (MFIS) relative change was calculated. Quality of Life (QoL) improved in Alfacalcidol-treated patients as compared with placebo in the RAYS psychological (p=0.033) and social (p=0.043) sub-scales. The Alfacalcidol- treated group had reduced number of relapses (p=0.006) and higher proportion of relapse-free patients (p=0.007). Reduction of relapses by Alfacalcidol became significant at 4 months of treatment, was sustained at 6 months and decayed 2 months after drug discontinuation. Alfacalcidol treatment was safe and no serious adverse events were recorded. Conclusion: Alfacalcidol is a safe and effective treatment strategy to decrease fatigue and improve QoL in patients with MS.

Original languageAmerican English
Pages (from-to)767-775
Number of pages9
JournalMultiple Sclerosis Journal
Issue number6
StatePublished - 4 May 2015
Externally publishedYes

Bibliographical note

Funding Information:
The study was supported by an unrestricted research grant from Teva Pharmaceuticals Ltd., Israel. The sponsor had no role in the study design, data collection, data analysis, interpretation, writing of the manuscript, or the decision to submit the manuscript for publication.

Publisher Copyright:
© The Author(s), 2014.


  • Alfacalcidol
  • Multiple sclerosis
  • Quality of Life
  • clinical trial
  • fatigue


Dive into the research topics of 'Effect of Alfacalcidol on multiple sclerosis-related fatigue: A randomized, double-blind placebo-controlled study'. Together they form a unique fingerprint.

Cite this