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Restless Legs Syndrome (RLS) is a common neurological sensorimotor disorder defined by an urge to move the legs when at rest that increase in the evening and at night. The pathophysiology of RLS remains poorly understood, but brain iron deficiency plays a major role. Iron absorption is an active process located in enterocytes of the proximal bowel, and is inhibited by hepcidin. The gut microbiota plays a central role in intestinal absorption, and in the maturation of the immune system. An imbalance in the microbiota, known as dysbiosis, could lead to a decrease in iron absorption, inflammation of the intestinal epithelium, and an increase in its permeability, thus favoring bacterial translocation and chronic systemic inflammation. Numerous studies showed an association between RLS and gastrointestinal diseases: Irritable bowel syndrome, Crohn's disease, ulcerative colitis, small intestinal bacterial overgrowth. However, no study has examined the gut microbiota in RLS.
The investigators hypothesize that there is an imbalance of gut microbiota in patients with RLS, favoring an increased intestinal permeability and bacterial translocation, leading to chronic inflammation and reduced iron bioavailability.
Sixty patients with RLS will be included and 60 controls. The patients will be recruited from the active file of the sleep and wake disorders unit.
The control subjects will be recruited from :
The patients will be informed of the study during a medical consultation. The consent of subjects participating in the study will be obtained during the pre-inclusion visit (D-1). The referring physician of the patients with RLS will propose them to participate in the study. After being duly informed of the nature, significance, implications of the study and appropriately documented by one of the investigators, and after sufficient time for reflection, free, informed and written consent will be obtained from all patients.
The control subjects will receive information about the study when they are admitted to hospital for polysomnographic recording, they will sign their consent for. A clinical examination will also be carried out.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients |
| ||
| Control |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fecal collection | Other | approximate volume of 2 ml |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Taxonomic composition of gut microbiota | Diversity (alpha and beta), abundance, nature and relative quantification of bacterial genera and bacterial taxonomic units (OTUs) present in stool samples identified by metagenomics. | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Ratio between Firmicutes and Bacteroidetes (majority phyla) | Richness, diversity and importance of minority phyla in stools, distribution and importance of bacterial genera in patients and controls. The study of the intestinal microbiota will consist of a metabarcoding approach to the V3-V4 regions of the 16S rRNA. | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Markers of intestinal inflammation (CD14s, LBP) | The study of bacterial translocation will be carried out using the ELISA technique for intestinal inflammation markers. | 24 months |
| Markers of digestive permeability (I-FABP, claudine) |
Inclusion Criteria:
Patient
Exclusion Criteria:
Patient
Inclusion Criteria:
Control
Exclusion Criteria:
Control
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60 patients with RLS and 60 controls meeting all criteria, with the aim of having 50 analyzable subjects per group (i.e. with available stool samples).
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| CHENINI Sofiene, Dr | Contact | 0467332237 | 33 | s-chenini@chu-montpellier.fr |
| DAUVILLIERS Yves, Pr | Contact | 0467337478 | y-dauvilliers@chu-montpellier.fr |
| Name | Affiliation | Role |
|---|---|---|
| DAUVILLIERS Yves, Pr | Head of Sleep/Wake Unit National reference center for orphan diseases Narcolepsy and hypersomnia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Unité des troubles du sommeil et de l'éveil-Centre de référence narcolepsie-Hypersomnie/Département de Neurologie/ Pole neurosciences tête et cou Hôpital Gui De Chauliac | Recruiting | Montpellier | 34295 | France |
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| ID | Term |
|---|---|
| D012148 | Restless Legs Syndrome |
| ID | Term |
|---|---|
| D009422 | Nervous System Diseases |
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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| Blood sampling |
| Other |
1 EDTA tube (7 ml) to test for chronic low-grade inflammation + 1 EDTA tube (7 ml) to test for intestinal inflammation, digestive permeability and microbial translocation |
|
| Polysomnography | Other | Polysomnography |
|
| Auto questionnaires | Other | International RLS Study Group Severity Scale, Epworth Sleepiness Scale, Insomnia Severity Index, Beck Depression Inventory-II, Autonomic symtoms scale (SCOPA-AUT) |
|
The study of bacterial translocation will be carried out using the ELISA technique for markers of membrane permeability.
| 24 months |
| Markers of microbial translocation (16S et 18SrDNA) | The study of bacterial translocation will be carried out using 16S and 18S qPCR for direct translocation markers. | 24 months |
| Correspondence between bacteria identified by relative quantification of bacterial genera and OTUs present in stools and those detected by qPCR in plasma. | Identification of the concordance between bacterial genera identified in plasma and bacterial genera and OTUs present in stools will be done using Spearman's correlation coefficient. | 24 months |
| D020447 |
| Parasomnias |
| D001523 | Mental Disorders |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |