Restless Legs Syndrome (RLS)
Conditions
Keywords
Ferric carboxymaltose, periodic legs movements, intractable restless legs
Brief summary
The pathophysiology of restless legs syndrome (RLS) is not well understood: it is thought to involve intracerebral iron deficiency and dopaminergic dysregulation. This study aims to evaluate the use of intravenous ferric carboxymaltose in patients with restless legs syndrome (RLS). This study plans to include individuals with RLS, who will be divided into two groups: * One group will receive intravenous iron immediately after the baseline polysomnography * The second group will receive intravenous iron 3 months after randomization. In total, participants will be followed for 6 months, during which time they will be required to complete questionnaires regularly, undergo blood draws, and have two polysomnography tests.
Interventions
administration of 1 g of CMF for 2 hours under medical monitoring
OTHERRandomization
Randomization in the arm "Immediate treatment" or "Delayed-onset treatment"
OTHERQuestionnaire and Physical Exam
Completion of questionnaires and scales: European Quality of Life 5 Dimensions (EQ-5D), Epworth Sleepiness Scale (ESS), Clinical Global Impression (CGI), Patient Global Impression (PGI), Beck Depression Inventory-II (BDI-II), Augmentation Severity Rating Scale (ASRS), International Restless Legs Study Group Severity Rating Scale (IRLSSG-Q), International Restless Legs Syndrome (IRLS), Insomnia Severity Index (ISI)
PROCEDURElumbar puncture
Lumbar puncture performed according to standard practice
PROCEDUREurine pregnancy test
During inclusion visit (Day 0) only for women of childbearing age
Sponsors
University Hospital, Montpellier
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years; * Weight ≥ 50 kg; * Drug-resistant RLS; * Severe to very severe RLS (IRLSSG-Q score \> 20), persistent or recurrent for more than one month; * Treatment with dopamine agonists without exceeding the recommended doses (ropinirole ≤ 2 mg/day, pramipexole ≤ 0.54 mg/day, rotigotine ≤ 3 mg/day); * Treatment with dopamine agonists and/or α2δ ligands and/or opioids that has been stable for at least 3 months; * In cases of sleep apnea syndrome, treatment with continuous positive airway pressure (CPAP); * Participants were required to be fluent in spoken and written French, be enrolled in a health insurance plan, agree to the automated processing of anonymized confidential data, and have provided written, informed consent for the study.
Exclusion criteria
* Iron supplementation (oral or intravenous) within 3 months prior to enrollment and throughout the study period * Serum ferritin \< 50 µg/L or \> 300 µg/L; * Transferrin saturation \< 20% or \> 45%; * Hemochromatosis; * RLS augmentation syndrome ; * Treatment with neuroleptics or antidepressants; * Allergy to iron; * Severe infectious or inflammatory disease within the past 3 months; * RLS associated with chronic kidney disease, pregnancy, or a clinically significant neurological or psychiatric disorder; * Severe sleep apnea syndrome (AHI \> 30/h) that is untreated, or in cases where treatment is refused or has failed; * Known allergy, inflammatory, or immune disorder; * History of severe asthma, eczema, or any other atopic allergy; * Pregnancy or breastfeeding; * Also excluded are patients participating in another research study, those deprived of their liberty by judicial or administrative order, those living in a medical facility, those subject to a legal protection order, or those from whom consent could not be obtained.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IRLSSG-Q score | From Day 0 to Week 12 | IRLSSG-Q : International Restless Legs Study Group Severity Rating Scale allows for the quantification of the severity of restless legs syndrome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Periodic Limb Movements during Sleep (PLMS) index | From V1 (Day 0) to V5 (week 24) | The PLMS Index measures the average number of involuntary leg movements per hour of sleeping during polysomnography. 15 or more per hour: Considered abnormal for adults and may suggest a condition called Periodic Limb Movement Disorder (PLMD) if it disrupts your sleep. |
| Total sleep time | From day 0 to week 24 | Total sleep time measured in minutes during polysomnography. |
| Sleep latency | From Day 0 to week 24 | Length of time in minutes it takes to transition from full wakefulness to the lightest stage of sleep after the lights are turned off. |
| Sleep time at stage 1-2 during polysomnography | From Day 0 to week 24 | Time spent in stage 1-2 sleep measured in hours and minutes during polysomnography |
| Sleep time at stage 3 during polysomnography | From Day 0 to week 24 | Time spent in stage 3 sleep measured in hours and minutes during polysomnography |
| Micro-awakenings index (MAI) | From Day 0 to week 24 | The Micro-awakenings index measures the number of brief awakenings that the person does not notice per hour of sleep. |
| Apnea-hypopnea index (AHI) | From Day 0 to week 24 | The apnea-hypopnea index (AHI) measures the average number of interruptions or reductions in breathing per hour of sleep to assess the severity of sleep apnea. |
| Average arterial oxygen saturation (SaO2) | From Day 0 to Week 24 | The unit of measurement for SaO2 is the percentage (%). |
| Oxygen desaturation index (IDO) | From Day 0 to week 24 | The oxygen desaturation index (IDO) measures the number of significant drops in blood oxygen levels per hour of sleep. |
| Serum ferritin | From Day 0 to week 24 | — |
| Transferrin saturation coefficient | From Day 0 to Week 24 | — |
| Epworth Sleepiness Scale (ESS) | From Day 0 to Week 24 | A measure of excessive daytime sleepiness that quantifies the impact of the condition on alertness throughout the day. Eight everyday situations are rated (for example, watching television, riding as a passenger in a car, sitting quietly in a public place). Each situation is scored from 0 to 3 based on the likelihood of falling asleep. Total score 0-24; a score of ≥10 suggests excessive sleepiness |
| European Quality of Life 5 Dimensions (EQ-5D) | From Day 0 to Week 24 | EQ-5D: this self-administered questionnaire assesses five dimensions (mobility, daily activities, self-care, pain/discomfort, anxiety/depression) as well as overall health status on a visual scale from 0 to 100 |
| Clinical Global Impression (CGI) | From Day 0 to Week 24 | The clinician's overall assessment of the illness, including CGI-S (severity) and CGI-I (change). 7-point scale: CGI-S 1 = normal, 7 = extremely ill; CGI-I 1 = markedly improved, 7 = markedly worsened |
| Patient Global Impression (PGI) | From Day 0 to Week 24 | Patient's overall perception of the severity of their illness or change; a simple 7-point scale, self-reported. A high score is associated with patients perceiving their symptoms as severe |
| Beck Depression Inventory-II (BDI-II) | From Day 0 to Week 24 | BDI-II: a self-administered questionnaire consisting of 21 items that assess the severity of depressive symptoms over the past two weeks; score range: 0-63; thresholds: 0-13 (mild), 14-19 (moderate), 20-28 (severe), ≥29 (severe) |
| Augmentation Severity Rating Scale (ASRS) | From Day 0 to Week 24 | A 7-item self-administered questionnaire used to quantify the severity of the augmentation syndrome in patients treated with dopamine agonists. It assesses the worsening or early onset of RLS symptoms and their impact on sleep and daily activities |
| Insomnia Severity Index (ISI) | From Day 0 to week 24 | To assess the severity of the patient's insomnia, taking into account both the quantity and quality of sleep, as well as its impact on daily functioning (fatigue, concentration, mood). A 7-item self-report questionnaire scored from 0 to 4, with a total score of 0-28; 0-7 indicates no insomnia, 8-14 mild, 15-21 moderate, and 22-28 severe insomnia |
Countries
France
Contacts
CONTACTYves DAUVILLIERS, MD - PhD
Outcome results
None listed