METAglut1: Early Diagnosis of the GLUT1 Deficiency Syndrome With a Blood Based Test

Sponsor

METAFORA biosystems (Industry)

Overall Status

Completed

CT.gov ID

NCT03722212

Collaborator

European Commission (Other), Assistance Publique - Hôpitaux de Paris (Other), Cemka-Eval (Other), Ministry for Health and Solidarity, France (Other), French National Authority for Health (Other)

650

Enrollment

Locations

Arm

30.2

Actual Duration (Months)

21.7

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glut1 Deficiency Syndrome De Vivo Disease Seizures Movement Disorders Intellectual Disability Ataxia	Diagnostic Test: METAglut1	N/A

Detailed Description

The GLUT1 Deficiency Syndrome (GLUT1-DS) 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 GLUT1-DS early, based on symptoms associated with GLUT1-DS, 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 GLUT1-DS 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 GLUT1-DS.

METAglut1 is a first-in-kind IVD device used to aid in the diagnosis of the GLUT1 Deficiency Syndrome (GLUT1-DS) 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 GLUT1-DS 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 GLUT1-DS 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

650 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

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.The METAglut1 test is performed on each patient, in parallel and blindly of the reference diagnostic strategy which is performed through the current practice.

Masking:

None (Open Label)

Masking Description:

The METAglut1 test is performed blindly of the reference strategy. METAglut1's result masking is maintained for the investigator on the one hand, and the glycorrhachia value masking is maintained for the centralized testing laboratory in charge of METAglut1 on the other hand.

Primary Purpose:

Diagnostic

Official Title:

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

Actual Study Start Date :

Sep 24, 2018

Actual Primary Completion Date :

Mar 31, 2021

Actual Study Completion Date :

Mar 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Other: Patients for 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. Already diagnosed patients are included retrospectively.	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.

Arm

Intervention/Treatment

Other: Patients for 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. Already diagnosed patients are included retrospectively.

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.

Outcome Measures

Primary Outcome Measures

Concordance analysis of 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.

Secondary Outcome Measures

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.

Other Outcome Measures

Sensitivity, specificity of METAglut1 [Up to 6 moths]
These analysis will be performed on patients with a diagnosis of certainty in the retrospective cohort.
Time to diagnosis [Up to 6 months]
The time between clinical suspicion of GLUT1-DS and diagnosis will be calculated and compared between different diagnostic strategies
Health technology assessment [Up to 2 years]
Health technology assessment will be performed on patients included in the study

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Months and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Clinical suspicion of the GLUT1 Deficiency Syndrome

Exclusion Criteria:

Sickle cell disease S/S
Abnormal imaging

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hôpital Larrey- CHU Angers	Angers	France	49933
2	Hôpital Saint Léon	Bayonne	France	64109
3	Hôpital Jean Verdier- APHP	Bondy	France	93140
4	Centre hospitalier Pellegrin_ CHU Bordeaux	Bordeaux	France	33076
5	Hôpital Morvan_ CHU Brest	Brest	France
6	Hôpital Femme Mere enfant- CHU de Lyon	Bron	France	69677
7	Hospices Civils de Lyon_CHU Lyon	Bron	France
8	Hôpital d'Estaing- CHU Clermont-Ferrand	Clermont-Ferrand	France	63003
9	CHU Dijon Bourgogne	Dijon	France	21079
10	Hôpital Raymond Poincaré- APHP	Garches	France
11	Hôpital Nord_CHU Grenoble	La Tronche	France	38700
12	Hôpital Jeanne de Flandre _CHRU Lille	Lille	France
13	Hôpital de la mère et de l'enfant- CHU Limoges	Limoges	France	87042
14	Hôpital La Timone Enfant- APHM	Marseille	France	13385
15	CHR Metz-Thionville	Metz	France	57085
16	Hôpital Gui de Chauliac- CHU Montpellier	Montpellier	France	34295
17	Hôpital Mère-Enfant_ CHU de Nantes	Nantes	France
18	Hôpital la Pitié-Salpêtrière-APHP	Paris	France	75013
19	Hôpital Necker- APHP	Paris	France	75015
20	Hôpital Robert Debré- APHP	Paris	France	75019
21	Hôpital Trousseau- APHP	Paris	France	75571
22	Hôpital Bicêtre- APHP	Paris	France
23	Hôpital Sud de Rennes- CHU Rennes	Rennes	France	35203
24	Hôpital de Saint-Nazaire	Saint-Nazaire	France	44606
25	Hôpital Nord, CHU Saint-Etienne	Saint-Priest-en-Jarez	France	42270
26	Hôpital de Hautepierre- CHU Strasbourg	Strasbourg	France
27	Hôpital de Tarbes - CH Bigorre	Tarbes	France	65013
28	Hopital Purpan- CHU Toulouse	Toulouse	France	31059
29	Hôpital des Enfants- CHU Toulouse	Toulouse	France	31059
30	Hôpital de Clocheville_ CHU Tours	Tours	France	37000