The purpose of the study is to determine the relative effect size of standard IV and oral
iron treatment of RLS with Iron deficiency anemia (IDA) and to determine the time course of
The restless legs syndrome (RLS) (also known as Willis Ekbom Disease) occurs in about 1/3rd
of patients with iron deficiency anemia (IDA). Treatment correcting the IDA is expected to
also be effective for reducing or eliminating the RLS with IDA. Two accepted treatments for
IDA (oral ferrous sulfate, intravenous ferumoxytol) will be compared for efficacy and speed
to response for treatment of RLS occurring with IDA (RLS-IDA). In this study 70 RLS-IDA
patients will be randomly assigned 35 each to oral or IV iron treatment using double-blind
procedures. Primary outcome with be determined at 6 weeks of treatment with a follow-up at
12 months after treatment. Non-responders at 6 weeks after treatment may, if they qualify,
have an open-label IV iron treatment and they will be followed with the same evaluations
used after the first set of IV iron treatments.
Both oral and IV iron are considered standard treatments for IDA. These same treatments also
reduce RLS symptoms. The treatment doses are those accepted for treatment of RLS and also
appropriate for treatment for RLS-IDA. Choosing doses equivalent to those for the treatment
of RLS without IDA will allow a comparison with that literature. The investigators will
therefore use for oral iron ferrous sulfate 325mg taken twice a day matching the dose used
in the study of oral iron treatment for RLS without anemia. For IV iron investigators will
use ferumoxytol, provided by the sponsor, two doses of 510 mg spaced 2 to 7 days apart. This
is the FDA approved dose for treatment of IDA with end stage renal disease.
The study is a randomized, comparative open label study to evaluate effect size and time
course of treatment response for RLS-IDA over 6 weeks with a 46-week follow-up extension.
Two medications and placebos will be used, as described above, with equal random assignment
to both groups.
- Diagnosis of RLS based on questionnaire and confirmed by Hopkins telephone Diagnostic
Interview conducted by investigators or clinicians part of the study.
- Iron deficiency anemia defined as ID either ferritin <20 mcg/l, Tsat <19%, anemia Hgb
<13 for both males and females.
- Willingness to use contraceptive to avoid pregnancy: Women have to be surgically
sterile, post-menopausal, or use one of the following contraceptives during the whole
study period and after the study has ended for at least 5 times plasma biological
half-life of the investigational medicinal product: intrauterine devices or hormonal
contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal
devices, or injections with prolonged release).
- Willingness to participate and signing the informed consent form.
- Iron overload or disturbances in utilization of iron (e.g. haemochromatosis and
- Decompensated liver cirrhosis or active hepatitis (ALAT > 3 times upper limit of
- Serum ferritin > 500 ng/mL or transferrin saturation >40%
- Active acute or chronic infections (assessed by clinical judgement that may be
indicated by White Blood Cells (WBC) and C-Reactive Protein (CRP) when these are
- Rheumatoid arthritis with symptoms or signs of active inflammation
- Pregnant and nursing women
- History of multiple allergies
- Known hypersensitivity to parenteral or oral iron or any excipients in the drug
- Previous IV iron treatment for RLS
- Other iron treatment or blood transfusion within 4 weeks prior to the screening or
- Planned elective surgery during the study
- Current (past 4 weeks) use of drugs that treat RLS, e.g. opioids, alpha-2-delta
anti-depressants, dopaminergics (dopamine promoters, dopamine antagonists/blockers)
- Any other medical condition that, in the opinion of Investigator, may cause the
subject to be unsuitable for the completion og the study or place the subject at
potential risk from being in the study, e.g. a malignancy, uncontrolled hypertension,
unstable ischemic heart disease, or uncontrolled diabetes mellitus.
Michael Auerbach, MD
Auerbach Hematology and Oncology Associates, PC
Michael Auerbach, MD