Exploration of GCase Activity to Identify a Subpopulation Eligible for a Therapeutic Trial in Dementia With Lewy Bodies (EGELY)

Exploration of Glucocerebrosidase Activity to Identify a Subpopulation Eligible for a Therapeutic Trial in Dementia With Lewy Bodies

This research focuses on the activity of an enzymatic protein: glucocerebrosidase, in dementia with lewy bodies (DLB). Indeed, the mutation of the GBA gene responsible for a decrease in the activity of glucocerebrosidase is the most frequent known genetic risk factor in DLB. However, mutations of the GBA gene are known in another pathology, Gaucher disease, in which treatments have been developed.

The objective of this research is to determine if glucocerebrosidase activity is decreased in DLB. This hypothesis could open up a therapeutic perspective, with treatments already used in Gaucher disease.

Study Overview

• Status: Recruiting
• Conditions: Dementia With Lewy Bodies
• Intervention / Treatment: Diagnostic test: Glucocerebrosidase; Genetic: GBA gene

Detailed Description

Population: 118 patients and 118 control subjects Act of research: blood test

Objectifs :

• Comparison of glucocerebrosidase activity between patients and controls
• Search for variants or mutations of the GBA gene and correlation with glucocerebrosidase activity
• Correlation between clinical characteristics (UPDRS motor scale, MMSE cognitive scale) and GCase activity in patients

• Study Type: Observational
• Enrollment (Estimated): 236

Contacts and Locations

• Study Contact: Name: Claire HOURREGUE, MD; Phone Number: +33 0140054313; Email: claire.hourregue@aphp.fr
• Study Contact Backup: Name: Claire PAQUET, PhD; Phone Number: +33 0140054313; Email: claire.paquet@aphp.fr

Study Locations

• France
  • Paris, France, 75010
    • Recruiting
    • Centre de neurologie Cognitive
    • Contact: Claire HOURREGUE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

118 patients and 118 control subjects Patients and controls (often an accompanying person) will be selected during a routine visit for the patient's DLB

Description

Inclusion Criteria for patients :

• Male or female aged ≥ 50 years old
• Presence of an accompanying person
• Dementia with lewy bodies according to the revised criteria of Mc Keith 2017

Inclusion Criteria for controls:

• Male or female aged ≥ 50 years old
• Absence of cognitive impairment and clinical element for a neurodegenerative disease

Exclusion Criteria for patients:

• Other neurodegenerative disease
• Gaucher disease

Exclusion Criteria for controls:

• Neurodegenerative disease
• Cognitive impairment of all causes

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
DLB patients; Dementia with lewy bodies according to the revised criteria of Mc Keith 2017	Diagnostic test: Glucocerebrosidase; Blood sample (10ml) for GCase activity; Genetic: GBA gene; Blood sample (10ml) for variants or mutations of the GBA gene
Control; Absence of cognitive impairment and clinical element for a neurodegenerative disease	Diagnostic test: Glucocerebrosidase; Blood sample (10ml) for GCase activity; Genetic: GBA gene; Blood sample (10ml) for variants or mutations of the GBA gene

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GCase activity in patients and control by fluorometry	difference in measurement of glucocerebrosidase enzyme activity (by fluorometry method) between DLB patients and control subjects.	through study competion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GBA gene and GCase activity	correlation between the presence of GBA gene mutation and the measurement of glucocerebrosidase enzymatic activity	through study competion, an average of 1 year
MMSE score and GCase activity	correlation between the measurement of glucocerebrosidase enzymatic activity and MMSE score (Mini-Mental State Examination from 0-severe to 30-normal) of DLB patients	through study competion, an average of 1 year
motor sub-score of UPDRS score and GCase activity	correlation between the measurement of glucocerebrosidase enzymatic activity and motor sub-score of UPDRS score (motor sub-score of Unified Parkinson Disease Rating Scale from) of DLB patients The score is between 0 and 55. The score increases proportionally to the severity of the extrapyramidal syndrome.	through study competion, an average of 1 year

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: March 21, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Glucocerebrosidase; GBA gene
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dementia; Lewy Body Disease
• Other Study ID Numbers: APHP201175; 2021-A02345-36 (Other Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No