Early Diagnosis of the GLUT1 Deficiency Syndrome With a Blood Based Test

NCT ID: NCT03722212

Last Updated: 2022-12-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 636 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-24
• Study Completion Date: 2021-07-09

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.

Conditions

Glut1 Deficiency Syndrome; De Vivo Disease; Seizures; Movement Disorders; Intellectual Disability; Ataxia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Prospective patients

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.

Group Type: OTHER

METAglut1

Intervention Type: DIAGNOSTIC_TEST

A blood draw is performed on each patient for the METAglut1 test, and sent to Laboratoire CERBA, Saint-Ouen l'Aumône, France, for sample analysis.

Retrospective patients

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).

Group Type: OTHER

METAglut1

Intervention Type: DIAGNOSTIC_TEST

A blood draw is performed on each patient for the METAglut1 test, and sent to Laboratoire CERBA, Saint-Ouen l'Aumône, France, for sample analysis.

Interventions

METAglut1

A blood draw is performed on each patient for the METAglut1 test, and sent to Laboratoire CERBA, Saint-Ouen l'Aumône, France, for sample analysis.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Clinical suspicion of the GLUT1 Deficiency Syndrome

• Patients with confirmed Glut1DS diagnosis
• Patients with pending diagnosis at inclusion (inconsistent biological or genetic data)

Exclusion Criteria

• Patients under 3 months of age
• Sickle cell disease S/S
• Abnormal imaging

• Minimum Eligible Age: 3 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Commission

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: collaborator

Cemka-Eval

OTHER

Sponsor Role: collaborator

Ministry for Health and Solidarity, France

OTHER_GOV

Sponsor Role: collaborator

French National Authority for Health

UNKNOWN

Sponsor Role: collaborator

METAFORA biosystems

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fanny Mochel, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Hôpital Larrey- CHU Angers

Angers, , France

Hôpital Saint Léon

Bayonne, , France

Hôpital Jean Verdier- APHP

Bondy, , France

Centre hospitalier Pellegrin_ CHU Bordeaux

Bordeaux, , France

Hôpital Femme Mere enfant- CHU de Lyon

Bron, , France

Hospices Civils de Lyon_CHU Lyon

Bron, , France

Hôpital d'Estaing- CHU Clermont-Ferrand

Clermont-Ferrand, , France

CHU Dijon Bourgogne

Dijon, , France

Hôpital Raymond Poincaré- APHP

Garches, , France

Hôpital Nord_CHU Grenoble

La Tronche, , France

Hôpital Jeanne de Flandre _CHRU Lille

Lille, , France

Hôpital de la mère et de l'enfant- CHU Limoges

Limoges, , France

Hôpital La Timone Enfant- APHM

Marseille, , France

CHR Metz-Thionville

Metz, , France

Hôpital Gui de Chauliac- CHU Montpellier

Montpellier, , France

Hôpital Mère-Enfant_ CHU de Nantes

Nantes, , France

Hôpital la Pitié-Salpêtrière-APHP

Paris, , France

Hôpital Necker- APHP

Paris, , France

Hôpital Robert Debré- APHP

Paris, , France

Hôpital Trousseau- APHP

Paris, , France

Hôpital Bicêtre- APHP

Paris, , France

Hôpital Sud de Rennes- CHU Rennes

Rennes, , France

Hôpital de Saint-Nazaire

Saint-Nazaire, , France

Hôpital Nord, CHU Saint-Etienne

Saint-Priest-en-Jarez, , France

Hôpital de Hautepierre- CHU Strasbourg

Strasbourg, , France

Hôpital de Tarbes - CH Bigorre

Tarbes, , France

Hôpital des Enfants- CHU Toulouse

Toulouse, , France

Hôpital de Clocheville_ CHU Tours

Tours, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 28556183 (View on PubMed)

Related Links

http://www.metafora-biosystems.com

METAglut1's project website

Other Identifiers

2017-A01473-50

Identifier Type: -

Identifier Source: org_study_id