Intravenous iron in the management of drug-resistant restless legs syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Montpellier

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-05-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

France EKBOM

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of intravenous ferric carboxymaltose (FCM) 1000 mg administered according to AASM guidelines, compared with conventional management according to SFRMS recommendations, on the change in IRLSSG-Q score between the baseline visit (V1) and the 3-month follow-up visit (V3), in patients with pharmacoresistant restless legs syndrome (RLS).

Secondary objectives 6

1. To evaluate the efficacy of intravenous FCM on the periodic limb movement during sleep (PLMS) index in the immediate-treatment group between V1 and V3, and in the delayed-treatment group after treatment administration (V3–V5).
2. To evaluate the efficacy of intravenous FCM on other polysomnographic parameters in the immediate-treatment group between V1 and V3, and in the delayed-treatment group after treatment administration (V3–V5) (confirmatory analysis).
3. To evaluate the efficacy of intravenous FCM administered according to AASM guidelines compared with conventional management on changes in IRLSSG-Q scores according to baseline biological parameters related to iron metabolism at the peripheral (serum) and central (CSF) levels.
4. To evaluate the effect of intravenous FCM on serum biological parameters in the immediate-treatment group between V1 and V3, and in the delayed-treatment group after treatment administration (V3–V5) (confirmatory analysis).
5. To identify clinical, biological, and polysomnographic factors associated with a good response to intravenous FCM treatment.
6. To assess the efficacy of intravenous FCM on associated symptoms (daytime sleepiness, insomnia, depression) and quality of life by comparing changes from V1 to V3 between the immediate-treatment group and the delayed-treatment group.

Conditions and MedDRA coding

Restless legs syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age ≥ 18 years
2. Body weight ≥ 50 kg
3. Pharmacoresistant restless legs syndrome (RLS)
4. Severe to very severe RLS (IRLSSG-Q score >20), persistent or recurrent for more than one month
5. Treatment with dopamine agonists without exceeding recommended doses (ropinirole ≤ 2 mg/day, pramipexole ≤ 0.54 mg/day, rotigotine ≤ 3 mg/day)
6. Stable treatment with dopamine agonists and/or α2δ ligands and/or opioids for at least 3 months
7. In the presence of sleep apnea syndrome, treatment with continuous positive airway pressure (CPAP)
8. Fluent in spoken and written French
9. Agree to the automated processing of anonymized confidential data
10. Be affiliated with a health insurance system
11. Written informed consent for participation in the study

Exclusion criteria 18

1. Iron supplementation (oral or intravenous) within the 6 months prior to inclusion and throughout the study period
2. Serum ferritin <50 µg/L or >300 µg/L
3. Transferrin saturation coefficient <20% or >45%
4. Hemochromatosis
5. Augmentation syndrome in RLS
6. Treatment with antipsychotics or antidepressants
7. Known iron allergy
8. Severe infectious or inflammatory disease within the previous 3 months
9. RLS associated with chronic kidney disease, pregnancy, or a clinically significant neurological or psychiatric disorder
10. Severe obstructive sleep apnea (apnea–hypopnea index >30/h) that is untreated, or in cases of refusal or failure of treatment
11. Known allergy, inflammatory or immune disorder
12. History of severe asthma, eczema, or any other atopic disease
13. Pregnancy or breastfeeding
14. Ongoing participation in a clinical study
15. Deprived of liberty by judicial or administrative decision
16. Living in a medicalized institution
17. Under legal protection
18. Failure to obtain consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome measure is the change in the IRLSSG-Q score between visit V1 (baseline) and visit V3 (3 months after V1).

Secondary endpoints 6

1. Change in the PLMS index between V1 and V3 in the immediate-treatment group and between V3 and V5 in the delayed-treatment group
2. Change in other polysomnographic parameters (total sleep time, wake after sleep onset, percentage of slow-wave sleep, and rapid eye movement sleep) between V1 and V3 in the immediate-treatment group and between V3 and V5 in the delayed-treatment group.
3. Serum biological parameters [between V1 and V3 in the immediate-treatment group and between V3 and V5 in the delayed-treatment group] and cerebrospinal fluid (CSF) parameters [at V1 in the immediate-treatment group and at V3 in the delayed-treatment group]: ferritin and transferrin saturation.
4. CSF biological parameters prior to intravenous FCM infusion in the immediate-treatment group (V1) and in the delayed-treatment group (V3): ferritin and transferrin saturation.
5. Clinical response defined as a decrease of ≥3 points in the IRLSSG-Q score between V1 and V3
6. Change in ESS, ISI, BDI, ASRS, and EQ-5D scores between V1 and V3 in the immediate-treatment group and between V3 and V5 in the delayed-treatment group.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Montpellier

Sponsor organisation

Centre Hospitalier Universitaire De Montpellier

Address

191 Avenue Du Doyen Gaston Giraud

City

Montpellier Cedex 5

Postcode

34295

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Montpellier

Contact name

Clinical project manager

Public contact point

Organisation

Centre Hospitalier Universitaire De Montpellier

Contact name

Clinical project manager

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications