A randomized, double-blind, placebo-controlled trial of intravenous iron sucrose in restless legs syndrome

Sleep Med. 2009 Feb;10(2):206-11. doi: 10.1016/j.sleep.2007.12.006. Epub 2008 Feb 14.


Objective: The aim of this study was to ascertain whether high-dose intravenous (IV) iron sucrose could improve symptoms and change brain iron concentrations in idiopathic RLS.

Methods: The study was a randomized, parallel-group double-blind study of 1000mg iron sucrose given IV versus placebo. Primary measures of the clinical status were global rating scale (GRS) and periodic leg movements of sleep (PLMS). Primary measures of brain iron status were CSF ferritin and MRI-determined iron in the substantia nigra.

Results: At the time of the interim analysis there were 7 placebo and 11 iron-treated subjects. At 2-weeks post-treatment, iron treatment resulted in a small but significant increase in CSF ferritin and a decrease in RLS severity (GRS) but did not change PLMS or MRI iron index. None of the secondary outcomes changed with treatment. There was no single case of clear treatment benefit in any of the patients. This interim analysis revealed an effect size that was too small to allow for adequate power to find significant differences with the planed 36-subject enrollment for either the primary objective outcome of PLMS or any of the secondary outcomes. The study was stopped at this planned break-point given the lack of both adequate power and any indication for clinically significant benefit.

Conclusions: High-dose IV iron failed to demonstrate the robust changes reported in three prior open-label studies. Differences in iron formulation, dosing regiment, and peripheral iron status may explain some of the discrepancies between this and previous IV iron treatment studies.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Ferric Compounds / therapeutic use*
  • Ferric Oxide, Saccharated
  • Ferritins / cerebrospinal fluid
  • Glucaric Acid
  • Hematinics / therapeutic use*
  • Humans
  • Infusions, Intravenous
  • Iron / metabolism
  • Male
  • Middle Aged
  • Restless Legs Syndrome / drug therapy*
  • Restless Legs Syndrome / metabolism
  • Substantia Nigra / metabolism
  • Treatment Failure


  • Ferric Compounds
  • Hematinics
  • Ferritins
  • Iron
  • Ferric Oxide, Saccharated
  • Glucaric Acid