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

Seizures Clinical Trial

— METAglut1  

Official title:

Evaluation of METAglut1 Diagnostic Test Performances in Patients With a Clinical Suspicion of GLUT1 Deficiency Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03722212
• Other study ID #: 2017-A01473-50
• Status: Completed
• Phase: N/A
• Start date: September 24, 2018
• Est. completion date: July 9, 2021

Study information

• Verified date: August 2022
• Source: METAFORA biosystems
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 636
• Est. completion date: July 9, 2021
• Est. primary completion date: March 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months and older

Eligibility

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

Related Conditions & MeSH terms

• Ataxia
• Carbohydrate Metabolism, Inborn Errors
• De Vivo Disease
• Glut1 Deficiency Syndrome
• Intellectual Disability
• Movement Disorders
• Seizures
• Syndrome

Intervention

Diagnostic Test:
• 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.

Locations

Country	Name	City	State
France	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 Bicêtre- APHP	Paris
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 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

Sponsors (6)

Lead Sponsor	Collaborator
METAFORA biosystems	Assistance Publique - Hôpitaux de Paris, Cemka-Eval, European Commission, French National Authority for Health, Ministry for Health and Solidarity, France

Country where clinical trial is conducted

France, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sensitivity, specificity of METAglut1	These analysis will be performed on patients with a diagnosis of certainty in the retrospective cohort and cumulated cohort (prospective and retrospective). 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.	Up to 6 moths
Other	Concordance analysis between METAglut1 and glycorrhachia	This analysis will be performed on patients with at least lumbar puncture and METAglut1 testing and with a diagnosis of certainty, either positive or negative, in the cumulative cohort (prospective and retrospective).	Up to 6 months
Other	Sensitivity analysis with optimized threshold of positivity of the METAglut1™ assay	In a sensitivity analysis, the threshold of positivity of the METAglut1™ assay will vary between 75% and 80% and performances calculations will be reported for this variation.	Up to 6 months
Other	Time to diagnosis	The time between clinical suspicion of Glut1DS and diagnosis will be calculated and compared between different diagnostic strategies	Up to 6 months
Other	Health technology assessment	Health technology assessment will be performed on patients included in the study	Up to 2 years
Primary	Concordance analysis between METAglut1 and glycorrhachia	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.	Up to 6 months
Secondary	Sensitivity, specificity, positive and negative predictive values of METAglut1	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.	Up to 6 months

External Links

•   METAglut1's project website