Early Diagnosis of the GLUT1 Deficiency Syndrome With a Blood Based Test
- Conditions
- De Vivo DiseaseGlut1 Deficiency SyndromeMovement DisordersAtaxiaIntellectual DisabilitySeizures
- Interventions
- Diagnostic Test: METAglut1
- Registration Number
- NCT03722212
- Lead Sponsor
- METAFORA biosystems
- Brief Summary
The study aims at validating the diagnostic performances of the METAglut1, a blood in vitro diagnostic test, for the simple and early diagnosis of the Glut1 deficiency syndrome (Glut1DS, or De Vivo disease).
The blood test will be carried out prospectively on patients presenting with a clinical suspicion of Glut1DS, blindly from the reference strategy, which consists in a lumbar puncture for glycorrhachia measurement, completed by a molecular analysis.
The study will be conducted in more than 40 centers in France on up to 3,000 patients for 2 years.
- Detailed Description
The Glut1 Deficiency Syndrome (Glut1DS) is a debilitating, proteiform neurometabolic disorder caused by an impairment in the glucose transporter Glut1 at the cell surface. Patients suffer from seizures, movement disorders and intellectual disabilities. A timely diagnosis is of prime importance as this haploinsufficiency can be improved by the so-called ketogenic diet.
By diagnosing Glut1DS early, based on symptoms associated with Glut1DS, healthcare providers can prescribe the Keto diet therapy early in the disease progression, which could prevent impairment of central nervous system function caused by the disease. Therefore, an early diagnosis of Glut1DS for its treatment is crucial.
Currently, the disease is very difficult to diagnose correctly and in a timely manner. The current diagnosis practice requires a lumbar puncture in order to determine if hypoglycorrhachia occurs. The diagnosis result is then supported by the detection of a heterozygous pathogenic variant in slc2a1 gene. This diagnosis procedure is time consuming, expensive, and requires a geneticist's data interpretation. Currently, ketogenic diet therapy is the most efficient therapy for Glut1DS.
METAglut1 is a first-in-kind IVD device used to aid in the diagnosis of the Glut1 Deficiency Syndrome (Glut1DS) by quantifying the cell surface expression level of the glucose transporter 1 (Glut1) on circulating human red blood cells. The METAglut1 IVD is primarily intended for use in pediatric patients older than 3 months, of both sexes, of any ethnic origin. The METAglut1 IVD may also be used to aid in the diagnosis of Glut1DS in adults with late onset symptoms.
The METAglut1 IVD is authorized for marketing in the European Union pursuant to the CE mark and is currently being distributed in France.
The study aims to validate the diagnostic performances of METAglut1. It will last for 2 years, more than 40 centers will participate in the study across France. Up to 3,000 patients with symptoms compatible with Glut1DS will be included prospectively; each of them will be tested for METAglut1, in parallel and blindly of the reference strategy. The METAglut1 test is performed by Laboratoire CERBA (Saint-Ouen l'AumĂ´ne, France). A retrospective cohort of already diagnosed patients will also be analyzed to add more data. Concordance analysis with the glycorrhachia, the first biochemical dosage involved in the reference strategy, will be performed, and overall diagnostic performances of METAglut1 calculated.
Before to start analysis, a thorough data management plan was implemented with on-site monitoring, automated controls of eCRF and recoding after queries and data reviewing.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 636
- Clinical suspicion of the GLUT1 Deficiency Syndrome
Retrospective patients - Inclusion Criteria:
- Patients with confirmed Glut1DS diagnosis
- Patients with pending diagnosis at inclusion (inconsistent biological or genetic data)
Exclusion Criteria (for both cohorts):
- Patients under 3 months of age
- Sickle cell disease S/S
- Abnormal imaging
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Prospective patients METAglut1 The METAglut1 test is performed on all patients included in the study. In parallel, patients included prospectively (based on a clinical suspicion) benefit from the reference diagnostic strategy through the current practice, starting with a lumbar puncture for glycorrhachia dosage. Retrospective patients METAglut1 Patients with confirmed Glut1DS diagnosis Already diagnosed patients are included retrospectively as well as patients with pending diagnosis at inclusion (inconsistent biological or genetic data).
- Primary Outcome Measures
Name Time Method Concordance analysis between METAglut1 and glycorrhachia Up to 6 months This analysis will be performed on patients with a diagnosis of certainty, either positive or negative, in the prospective cohort. For this analysis two subgroups are distinguished:
* Patients with lumbar puncture, molecular analysis of the slc2a1 gene and METAglut1 testing.
* Patients with at least lumbar puncture and METAglut1 testing.
- Secondary Outcome Measures
Name Time Method Sensitivity, specificity, positive and negative predictive values of METAglut1 Up to 6 months These analysis will be performed on patients with a diagnosis of certainty in the prospective cohort. For this analysis two subgroups are distinguished:.
* Patients with at least lumbar puncture and METAglut1 testing.
* Patients with at least molecular analysis of the slc2a1 gene and METAglut1 testing.
Trial Locations
- Locations (28)
Centre hospitalier Pellegrin_ CHU Bordeaux
đŸ‡«đŸ‡·Bordeaux, France
HĂ´pital Nord, CHU Saint-Etienne
đŸ‡«đŸ‡·Saint-Priest-en-Jarez, France
HĂ´pital des Enfants- CHU Toulouse
đŸ‡«đŸ‡·Toulouse, France
HĂ´pital de Clocheville_ CHU Tours
đŸ‡«đŸ‡·Tours, France
HĂ´pital de Tarbes - CH Bigorre
đŸ‡«đŸ‡·Tarbes, France
HĂ´pital de Saint-Nazaire
đŸ‡«đŸ‡·Saint-Nazaire, France
HĂ´pital de Hautepierre- CHU Strasbourg
đŸ‡«đŸ‡·Strasbourg, France
HĂ´pital Larrey- CHU Angers
đŸ‡«đŸ‡·Angers, France
HĂ´pital Saint LĂ©on
đŸ‡«đŸ‡·Bayonne, France
HĂ´pital Jean Verdier- APHP
đŸ‡«đŸ‡·Bondy, France
HĂ´pital Femme Mere enfant- CHU de Lyon
đŸ‡«đŸ‡·Bron, France
Hospices Civils de Lyon_CHU Lyon
đŸ‡«đŸ‡·Bron, France
HĂ´pital d'Estaing- CHU Clermont-Ferrand
đŸ‡«đŸ‡·Clermont-Ferrand, France
CHU Dijon Bourgogne
đŸ‡«đŸ‡·Dijon, France
Hôpital Raymond Poincaré- APHP
đŸ‡«đŸ‡·Garches, France
HĂ´pital Nord_CHU Grenoble
đŸ‡«đŸ‡·La Tronche, France
HĂ´pital Jeanne de Flandre _CHRU Lille
đŸ‡«đŸ‡·Lille, France
Hôpital de la mère et de l'enfant- CHU Limoges
đŸ‡«đŸ‡·Limoges, France
HĂ´pital La Timone Enfant- APHM
đŸ‡«đŸ‡·Marseille, France
CHR Metz-Thionville
đŸ‡«đŸ‡·Metz, France
HĂ´pital Gui de Chauliac- CHU Montpellier
đŸ‡«đŸ‡·Montpellier, France
Hôpital Mère-Enfant_ CHU de Nantes
đŸ‡«đŸ‡·Nantes, France
HĂ´pital la PitiĂ©-SalpĂªtrière-APHP
đŸ‡«đŸ‡·Paris, France
HĂ´pital Necker- APHP
đŸ‡«đŸ‡·Paris, France
Hôpital Robert Debré- APHP
đŸ‡«đŸ‡·Paris, France
HĂ´pital Trousseau- APHP
đŸ‡«đŸ‡·Paris, France
HĂ´pital Sud de Rennes- CHU Rennes
đŸ‡«đŸ‡·Rennes, France
HĂ´pital BicĂªtre- APHP
đŸ‡«đŸ‡·Paris, France