Restless Legs SyndromePhase 2NCT02499354
Pilot Study: Randomized, Placebo-controlled Comparator Trial of IV vs Oral Iron Treatment of RLS With IDA. (IVOR-IDA)
A Phase 2 study testing Ferumoxytol intravenous and Ferrous sulfate in people with Restless Legs Syndrome and Iron Deficiency Anemia, run by Auerbach Hematology Oncology Associates P C at 1 site in United States.
Trial summary
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 treatment response. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Restless Legs Syndrome, Iron Deficiency Anemia
- What is being tested?
- Ferumoxytol intravenous and Ferrous sulfate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2014to 31 May 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Iron overload or disturbances in utilization of iron (e.g. haemochromatosis and haemosiderosis)
- Decompensated liver cirrhosis or active hepatitis (ALAT > 3 times upper limit of normal)
- 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 available)
- Rheumatoid arthritis with symptoms or signs of active inflammation
- Pregnant and nursing women
Show all 13Show fewer
- History of multiple allergies
- Known hypersensitivity to parenteral or oral iron or any excipients in the drug products
- Previous IV iron treatment for RLS
- Other iron treatment or blood transfusion within 4 weeks prior to the screening or treatment visit
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Auerbach Hematology Oncology Assoc
Baltimore, Maryland, 21237
About this study
Official title: Double-blind Comparator of Efficacy of Oral (Ferrous Sulfate) vs. Intravenous Iron (Ferumoxytol) for Treatment of the Restless Legs Syndrome (RLS) Occurring With Iron Deficient Anemia (IDA)
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 treatment response.
Read the detailed description
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.
- Conditions
- Restless Legs Syndrome, Iron Deficiency Anemia
- Being tested
- Ferumoxytol intravenous, Ferrous sulfate
- Medical subject headings
- Restless Legs Syndrome, Anemia, Iron-Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ferumoxytol intravenousDrug
Also called IV iron
IV iron, 2 vials of 510 mg given 2-7 days apart
Ferrous sulfateDrug
Also called Oral iron
Oral iron, 325 mg tabs taken morning and evening
| Study group | Role | What they receive |
|---|---|---|
| Oral Iron | Active comparator | Ferrous Sulfate 325mg (oral) tabs morning and evening Receives: Drug: Ferrous sulfate |
| IV Iron | Active comparator | Ferumoxytol intravenous (IV) 1020 mg - 2 vials of 510 mg (IV push, 2-3 mins) each given 2-7 days apart Receives: Drug: Ferumoxytol intravenous |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in the Restless Legs Syndrome Rating Scale
Change in International Restless Legs Severity Scale (IRLS) score reflecting RLS severity on the scale of 0-40. The higher the negative score the better the outcome
Measured: Baseline and at 6 weeks after treatment
Percentage of Participants With Improvement on Clinical Global Impression Scale
Seven questions ranging from Very Much Improved to Very Much Worse: Participant had to be at least Very Much Improved to be considered as having improved. The CGI scale consisted of one question.
Measured: Six weeks
Secondary outcomes (1)
Number of Participants With Adverse Events Judged Related or Possibly Related to Treatment.
Patient reported gastrointestinal or constitutional adverse events
Measured: Up to six weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2015 (estimated)
- Study startAug 2014
- Primary completion28 Sep 2021
- Study completion31 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Restless Legs SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Auerbach Hematology Oncology Associates P C
- Sponsor type
- University, hospital or other
- Collaborators
- AMAG Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Michael Auerbach MD, Auerbach Hematology Oncology Associates P C
- Investigators
- Michael Auerbach, MD, Principal investigator, Auerbach Hematology and Oncology Associates, PC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02499354
- Sponsor's protocol ID
- IVOR-IDA
- Status last verified
- Jan 2024
- First submitted
- 13 Jul 2015
- Last updated
- 30 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-blind Comparator of Efficacy of Oral (Ferrous Sulfate) vs. Intravenous Iron (Ferumoxytol) for Treatment of the Restless Legs Syndrome (RLS) Occurring With Iron Deficient Anemia (IDA)
- ClinicalTrials.gov ID
- NCT02499354
- Acronym / sponsor ID
- IVOR-IDA
- Conditions
- Restless Legs Syndrome, Iron Deficiency Anemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Auerbach Hematology Oncology Associates P CUniversity, hospital or other
- Collaborators
- AMAG Pharmaceuticals, Inc.
- Study start
- Aug 2014 (actual)
- Primary completion
- 28 Sep 2021 (actual)
- Study completion
- 31 May 2022 (actual)
- First posted
- 16 Jul 2015 (estimated)
- Results
- Posted 15 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 treatment response.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral Iron | Active comparator | Drug: Ferrous sulfateFerrous Sulfate 325mg (oral) tabs morning and evening |
| IV Iron | Active comparator | Drug: Ferumoxytol intravenousFerumoxytol intravenous (IV) 1020 mg - 2 vials of 510 mg (IV push, 2-3 mins) each given 2-7 days apart |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (13 listed)
- Iron overload or disturbances in utilization of iron (e.g. haemochromatosis and haemosiderosis)
- Decompensated liver cirrhosis or active hepatitis (ALAT > 3 times upper limit of normal)
- 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 available)
- Rheumatoid arthritis with symptoms or signs of active inflammation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ferumoxytol intravenousAlso: IV ironIV iron, 2 vials of 510 mg given 2-7 days apart | Drug | IV Iron |
| Ferrous sulfateAlso: Oral ironOral iron, 325 mg tabs taken morning and evening | Drug | Oral Iron |
Primary outcome
Change From Baseline in the Restless Legs Syndrome Rating Scale
Time frame: Baseline and at 6 weeks after treatment
Change in International Restless Legs Severity Scale (IRLS) score reflecting RLS severity on the scale of 0-40. The higher the negative score the better the outcome
Percentage of Participants With Improvement on Clinical Global Impression Scale
Time frame: Six weeks
Seven questions ranging from Very Much Improved to Very Much Worse: Participant had to be at least Very Much Improved to be considered as having improved. The CGI scale consisted of one question.
1 secondary outcome
Number of Participants With Adverse Events Judged Related or Possibly Related to Treatment.
Time frame: Up to six weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Auerbach, MD principal investigator
Auerbach Hematology and Oncology Associates, PC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ferumoxytol intravenous and Ferrous sulfate in people with Restless Legs Syndrome and Iron Deficiency Anemia, run by Auerbach Hematology Oncology Associates P C at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in the Restless Legs Syndrome Rating Scale (time frame: Baseline and at 6 weeks after treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2024.