Clinical trial NCT03722212: Early Diagnosis of the GLUT1 Deficiency Syndrome With a Blood Based Test
Official title: Evaluation of METAglut1 Diagnostic Test Performances in Patients With a Clinical Suspicion of GLUT1 Deficiency Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glut1 Deficiency Syndrome
De Vivo Disease
Seizures
Movement Disorders
Intellectual Disability
Ataxia
Keywords: Glut1 Deficiency Syndrome
Glut1DS
Lead sponsor: METAFORA biosystems
Sponsor class: INDUSTRY
Collaborators: name: European Commission
name: Assistance Publique - Hôpitaux de Paris
name: Cemka-Eval
name: Ministry for Health and Solidarity, France
name: French National Authority for Health
First posted: 2018-10-26
Enrollment: 636
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The METAglut1 test is performed on each patient, in parallel and blindly of the reference diagnostic strategy which is performed through the current practice (lumbar puncture (LP) performed in the fasting state with glycemia measured right before LP, followed by genetic analyses (targeted slc2a1 analysis or gene panels or whole exome sequencing).
Primary purpose: DIAGNOSTIC

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'Aumône, 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.

Eligibility criteria: Prospective patients - Inclusion Criteria:

* 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

Primary outcomes:
measure: Concordance analysis between METAglut1 and glycorrhachia
timeFrame: Up to 6 months
Secondary outcomes:
measure: Sensitivity, specificity, positive and negative predictive values of METAglut1
timeFrame: Up to 6 months
Other outcomes:
measure: Sensitivity, specificity of METAglut1
timeFrame: Up to 6 moths
measure: Concordance analysis between METAglut1 and glycorrhachia
timeFrame: Up to 6 months
measure: Sensitivity analysis with optimized threshold of positivity of the METAglut1™ assay
timeFrame: Up to 6 months
measure: Time to diagnosis
timeFrame: Up to 6 months
measure: Health technology assessment
timeFrame: Up to 2 years
Locations:
city: Angers
country: France
facility: Hôpital Larrey- CHU Angers
city: Bayonne
country: France
facility: Hôpital Saint Léon
city: Bondy
country: France
facility: Hôpital Jean Verdier- APHP
city: Bordeaux
country: France
facility: Centre hospitalier Pellegrin_ CHU Bordeaux
city: Bron
country: France
facility: Hôpital Femme Mere enfant- CHU de Lyon
city: Bron
country: France
facility: Hospices Civils de Lyon_CHU Lyon
city: Clermont-Ferrand
country: France
facility: Hôpital d'Estaing- CHU Clermont-Ferrand
city: Dijon
country: France
facility: CHU Dijon Bourgogne
city: Garches
country: France
facility: Hôpital Raymond Poincaré- APHP
city: La Tronche
country: France
facility: Hôpital Nord_CHU Grenoble
city: Lille
country: France
facility: Hôpital Jeanne de Flandre _CHRU Lille
city: Limoges
country: France
facility: Hôpital de la mère et de l'enfant- CHU Limoges
city: Marseille
country: France
facility: Hôpital La Timone Enfant- APHM
city: Metz
country: France
facility: CHR Metz-Thionville
city: Montpellier
country: France
facility: Hôpital Gui de Chauliac- CHU Montpellier
city: Nantes
country: France
facility: Hôpital Mère-Enfant_ CHU de Nantes
city: Paris
country: France
facility: Hôpital la Pitié-Salpêtrière-APHP
city: Paris
country: France
facility: Hôpital Necker- APHP
city: Paris
country: France
facility: Hôpital Robert Debré- APHP
city: Paris
country: France
facility: Hôpital Trousseau- APHP
city: Paris
country: France
facility: Hôpital Bicêtre- APHP
city: Rennes
country: France
facility: Hôpital Sud de Rennes- CHU Rennes
city: Saint-Nazaire
country: France
facility: Hôpital de Saint-Nazaire
city: Saint-Priest-en-Jarez
country: France
facility: Hôpital Nord, CHU Saint-Etienne
city: Strasbourg
country: France
facility: Hôpital de Hautepierre- CHU Strasbourg
city: Tarbes
country: France
facility: Hôpital de Tarbes - CH Bigorre
city: Toulouse
country: France
facility: Hôpital des Enfants- CHU Toulouse
city: Tours
country: France
facility: Hôpital de Clocheville_ CHU Tours
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Fanny Mochel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gras D, Cousin C, Kappeler C, Fung CW, Auvin S, Essid N, Chung BH, Da Costa L, Hainque E, Luton MP, Petit V, Vuillaumier-Barrot S, Boespflug-Tanguy O, Roze E, Mochel F. A simple blood test expedites the diagnosis of glucose transporter type 1 deficiency syndrome. Ann Neurol. 2017 Jul;82(1):133-138. doi: 10.1002/ana.24970.