Clinical trial NCT05304195: Exploration of GCase Activity to Identify a Subpopulation Eligible for a Therapeutic Trial in Dementia with Lewy Bodies
Official title: Exploration of Glucocerebrosidase Activity to Identify a Subpopulation Eligible for a Therapeutic Trial in Dementia with Lewy Bodies
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Dementia with Lewy Bodies
Keywords: Glucocerebrosidase
GBA gene
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2022-03-31
Enrollment: 236
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

Brief summary: 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.

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
* Identification of macrophage abnormalities and the impact of treatments targeting the GBA pathway on the deregulation of biomarkers in patient macrophages.

Eligibility criteria: 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

Primary outcomes:
measure: GCase activity in patients and control by fluorometry
timeFrame: through study competion, an average of 1 year
Secondary outcomes:
measure: GBA gene and GCase activity
timeFrame: through study competion, an average of 1 year
measure: MMSE score and GCase activity
timeFrame: through study competion, an average of 1 year
measure: motor sub-score of UPDRS score and GCase activity
timeFrame: through study competion, an average of 1 year
measure: GBA gene and macrophage abnormalities
timeFrame: through study competion, an average of 1 year
measure: Treatment and macrophage biomarkers
timeFrame: through study competion, an average of 1 year
Other outcomes:
Locations:
city: Paris
country: France
facility: Centre de neurologie Cognitive
Study officials:
References: