Intravenous ferric carboxymaltose for drug‑resistant restless legs syndrome: a randomized delayed‑start trial in adults

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What is this study about?

The study focuses on people with drug‑resistant Restless legs syndrome, a condition that causes uncomfortable sensations in the legs and a strong urge to move them, especially during periods of rest or sleep. The treatment being tested is an infusion of ferric carboxymaltose, a form of iron that is given through a vein, and it is compared with the usual care that follows current recommendations. The purpose of the study is to determine whether this iron infusion can lessen the severity of the leg symptoms.

Participants are randomly placed into two groups: one receives the iron infusion soon after the first visit, while the other group waits for a short period before receiving the same infusion. All participants complete a questionnaire about their leg symptoms, sleep quality, mood, and daily functioning at the start of the study and again after about three months. Simple blood tests are done to check iron levels, and a brief overnight sleep recording may be performed to assess sleep patterns. The study follows each person for several months to see how the symptoms change after the treatment.

1 baseline assessment (visit v1)

the first study visit occurs shortly after joining the trial. during this visit, questionnaires that measure restless legs severity, sleepiness, insomnia, mood, attention, and quality of life are completed. blood samples are taken to measure iron levels, and a sample of cerebrospinal fluid may be collected. a sleep study may be performed to record leg movements and sleep patterns.

2 randomization to immediate or delayed treatment

after baseline assessments, participants are assigned by chance to either the immediate‑treatment group or the delayed‑treatment group. the assignment determines when the iron infusion will be given.

3 intravenous ferric carboxymaltose infusion (immediate group)

participants in the immediate‑treatment group receive a single infusion of ferric carboxymaltose at a dose of 1000 mg. the medication is delivered through a vein over about fifteen minutes. no further doses are scheduled during the trial.

4 3‑month follow‑up visit (visit v3)

three months after the baseline visit, all participants return for a second evaluation. the same questionnaires, blood tests, and sleep study are repeated to assess changes. participants in the delayed‑treatment group receive the ferric carboxymaltose infusion at this visit, using the same dose and administration method as described for the immediate group.

5 final assessment (visit v5)

approximately three months after visit v3, a final visit is conducted. questionnaires, blood tests, and sleep study are performed again to evaluate long‑term effects. no additional iron infusions are given.

Who Can Join the Study?

Be at least 18 years old.
Have a health insurance plan.
Sign a written consent form agreeing to join the study.
Weigh at least 50 kilograms (about 110 pounds).
Have restless legs syndrome that does not improve with usual medicines, called pharmacoresistant (meaning the condition does not respond to standard drug treatment).
Experience severe or very severe restless legs symptoms, shown by a score higher than 20 on the IRLSSG‑Q questionnaire (a survey that measures how bad the symptoms are) and have had these symptoms for more than one month.
Be taking a dopamine agonist medication (a drug that helps control movement) but not more than the recommended maximum doses: ropinirole ≤ 2 mg per day, pramipexole ≤ 0.54 mg per day, or rotigotine ≤ 3 mg per day.
Have been on a stable dose of dopamine agonists, α2δ ligands (a type of medicine used for nerve pain or restless legs), or opioids (strong pain‑relieving drugs) for at least three months without changes.
If you also have sleep apnea, you must be using a continuous positive airway pressure (CPAP) machine (a device that helps keep the airway open while you sleep).
Be fluent in spoken and written French.
Agree that your personal information can be processed in an anonymous and confidential way.

Who Cannot Join the Study?

Taking iron supplementation (iron pills or iron IV) within the 6 months before joining or during the study.
Having severe obstructive sleep apnea (a breathing problem during sleep) that is not treated, or refusing or failing treatment.
Having a known allergy, or an inflammatory (body swelling) or immune (body‑defense) disorder.
Having a history of severe asthma, eczema, or any other atopic (allergy‑related) disease.
Being pregnant or breastfeeding.
Already taking part in another clinical study.
Being deprived of liberty by a judicial or administrative decision (for example, being in jail).
Living in a medicalized institution such as a nursing home.
Being under legal protection or guardianship.
Unable to give consent (permission) to join the study.
Having blood iron levels measured as serum ferritin less than 50 µg/L or more than 300 µg/L.
Having a transferrin saturation (how much iron is bound to a transport protein) less than 20% or more than 45%.
Having hemochromatosis (a condition where the body stores too much iron).
Having augmentation syndrome in restless legs syndrome (worsening of symptoms due to medication).
Taking antipsychotic or antidepressant medicines.
Having a known iron allergy.
Having a severe infection or inflammatory disease within the previous 3 months.
Having restless legs syndrome linked to chronic kidney disease, pregnancy, or a clinically significant neurological (brain) or psychiatric (mental health) disorder.

Where you can join this trial?

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Other Sites

Site Name	City	Country	Status
Centre Hospitalier Universitaire De Montpellier	Montpellier	France

Trial status

Country	Status	Recruitment Start
France	Not yet recruiting	01.04.2026

Trial locations

Investigated drugs:

Ferric Carboxymaltose

Ferric carboxymaltose is an iron solution given through an IV (intravenous) drip. In this study it is used to raise the amount of iron in the body, because low iron levels can worsen restless‑legs symptoms. Participants receive the infusion at the start of the trial and again if needed, following the schedule recommended by sleep‑medicine guidelines. The goal is to see if adding iron improves the severity of restless‑legs compared with usual care.

Conventional management refers to the standard medicines and non‑drug strategies that doctors normally use for restless‑legs syndrome, following the recommendations of the French Society of Restless Legs (SFRMS). This may include drugs that affect dopamine, calcium channels, or other pathways, as well as lifestyle advice such as sleep hygiene and exercise. In the trial, this group receives the usual care without the IV iron, allowing researchers to compare the added benefit of the iron treatment.

Restless legs syndrome – Restless legs syndrome is a neurological condition that causes an uncomfortable urge to move the legs, often accompanied by tingling or crawling sensations. The sensations typically appear when a person is at rest, especially in the evening or night, and are relieved by movement. Over time, the urge may become stronger and affect sleep, leading to frequent awakenings. The condition can gradually spread to involve the arms or other parts of the body. Symptoms may fluctuate day to day, but they generally persist without treatment.

Trial ID:

2026-525613-31-00

Protocol code:

IRON-RLS

Trial Phase:

Therapeutic exploratory (Phase II)

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Intravenous ferric carboxymaltose for drug‑resistant restless legs syndrome: a randomized delayed‑start trial in adults

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?