A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome

Abstract

Background: Restless legs syndrome (RLS) is a common disorder in patients with end-stage renal disease (ESRD) that causes motor agitation and insomnia. Because RLS has been associated with iron deficiency, we sought to investigate the effects of intravenous (IV) iron dextran on symptoms of RLS in a double-blind placebo-controlled trial.

Methods: Patients determined to have RLS by International RLS Study Group criteria were administered either iron dextran, 1,000 mg, or normal saline IV in a blinded fashion. Patient demographic data were collected, and blood chemistry tests, liver function studies, serum iron levels, ferritin levels, and total iron-binding capacity were obtained at baseline and 1, 2, and 4 weeks postinfusion. Side effects or adverse events to interventions were monitored, and RLS symptoms were assessed by a rating scale at the same intervals.

Results: Eleven patients were randomly assigned to the administration of iron dextran, and 14 patients to the administration of saline. RLS severity scores were slightly higher in the placebo group at baseline, but hemoglobin levels, iron stores, and other biochemical parameters did not differ. Although no change in symptoms were seen in the placebo-treated group, significant improvement in RLS symptom scores in response to iron dextran was seen 1 week after infusion (-2; interquartile range [IQR], -6 to -1; P = 0.03, Wilcoxon's rank sums), but was greatest at 2 weeks (-3; IQR, -5 to -2 compared with -1 to 0; P = 0.01). Salutary effects of iron persisted at 4 weeks, but were no longer statistically significant. The significant increase in serum ferritin levels and iron saturation observed in the iron dextran-treated group was not seen in the placebo-treated group. No differences in adverse events were noted between groups.

Conclusion: High-dose iron dextran infusion is associated with a significant, but transient, reduction in symptoms of RLS in patients with ESRD.