Towards the Validation of a New Blood Biomarker for the Early Diagnosis of Parkinson's Disease (BIOPARK)

Evaluation de la Performance Clinique d'un Nouveau Biomarqueur Sanguin Des Phases précoces de la Maladie de Parkinson

The investigators have recently discovered a metabolic biomarker which predicts Parkinson's disease (PD) at the early stages in patients and in animal models. The aim of BIOPARK is to investigate how the biomarker evolves in advanced PD stage, when diagnosis confirmation is higher, an in de novo PD patients who come from a different geographical area than those of the publication (since it is known that the metabolome is largely influenced by lifestyle). They will also evaluate if the biomarker is able to distinguish patients with a parkinsonian syndrome often confused with parkinson's disease, i.e. Multiple System Atrophy (MSA).

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease

Detailed Description

Parkinson's disease (PD) affects more than 7 million people worldwide and represents a growing health and socio-economic burden. It is an incurable neurodegenerative disease, and the search for biomarkers that allow reliable early diagnosis and provide new therapeutic targets is essential to find cures for PD.

In a recently published preclinical and clinical study, the investigators have identified in 2 rat models of PD and a primate model and in 2 human cohorts from biobanks significant deregulations of 6 serum metabolites: acetoacetate, betaine, beta-hydroxybutyrate, creatine, pyruvate and valine. From these 6 metabolites, they built a composite biomarker, which allowed to classify de novo parkinsonian patients against controls (healthy subjects) with an accuracy (defined as the ratio (correctly classified/total) of 82.6%. This study demonstrated for the first time that a common metabolic dysregulation occurs early in either animal models or in PD patients, thus providing an unbiased diagnostic tool as well as major hypothesis for the understanding of the pathophysiology of the disease and the development of innovative therapeutic approaches.

The goal of BIOPARK is to improve the clinical diagnosis of early PD using the blood biomarker.

To this end, the investigators will study whether the biomarker is able to differentiate between patients with PD >5 years and already treated with dopaminergic drugs (thus with a very high diagnostic confirmation) and patients suffering from other neurodegenerative diseases often confused with it, mainly Multiple Systeme Atrophy (MSA). Furthermore, the investigators hope to confirm the preliminary results on a new cohort of de novo patients.

For that aim, they will use the already optimized method for biomarker discovery, i.e. Nuclear Magnetic Resonance (NMR)-based metabolomics on patient serum.

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

• Study Contact: Name: Florence Fauvelle, PhD; Phone Number: (33)456520600; Email: florence.fauvelle@univ-grenoble-alpes.fr
• Study Contact Backup: Name: Andrea Kistner; Email: Akistner@chu-grenoble.fr

Study Locations

• France
  • Grenoble, France, 38043
    • Recruiting
    • CHU Grenoble Alpes
    • Contact: Florence FAUVELLE; Phone Number: +33 (0)4 56 52 06 00; Email: florence.fauvelle@univ-grenoble-alpes.fr
    • Contact: Andréa KRISTNER; Phone Number: +33 (0)4 76765791; Email: AKistner@chu-grenoble.fr
    • Principal Investigator: ELENA MORO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

The study population consists of patients coming for consultation or admission to day clinic of the neurologic department of the university hospital Grenoble.

Description

Inclusion Criteria:

• Patients with de novo Parkinson's disease, without dopaminergic treatment
• Patients with advanced Parkinson's disease (> 5years) with dopaminergic treatment
• Patients with multiple system atrophy

Exclusion Criteria:

• Patients with deep brain stimulation
• Other neurodegenerative diseases
• patients protected by french law (pregnant or lactating women, prisoners, ...)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Parkinson's Disease, de novo; patients with de novo PD, without dopaminergic treatment
Parkinson's Disease, advanced stage; PD patients with diagnosis >5years, with dopaminergic treatment and motor fluctuations.
Multiple system atrophy; patients with multiple system atrophy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
validation of the biomarker in advanced stage PD	The main objective of the project is to evaluate whether classification with the biomarker is consistent with the diagnosis in a cohort of parkinsonian patients with high diagnostic confirmation, i.e. patients treated with L-Dopa for over 5 years	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validation of the biomarker in a new cohort of PD patients	The first secondary objective is to assess whether the biomarker predicts disease in a new cohort of de novo parkinsonian patient	2 years
Specificity of the biomarker for PD	The second secondary objective is to assess the specificity of the blood biomarker for the differential diagnosis of PD (early and late stage) by measuring it in a patient population with probable AMS (which is a pathology confounding for PD)	2 years
Correlation with MDS-UPDRS	The third secondary objective is to assess, for all patients, whether the classification is consistent with the MDS-UPDRS motor score assessed at inclusion	2 years

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Collaborators: Grenoble Institut des Neurosciences
• Investigators: Principal Investigator: Elena Moro, University Hospital, Grenoble

Publications and helpful links

General Publications

• Mallet D, Dufourd T, Decourt M, Carcenac C, Bossu P, Verlin L, Fernagut PO, Benoit-Marand M, Spalletta G, Barbier EL, Carnicella S, Sgambato V, Fauvelle F, Boulet S. A metabolic biomarker predicts Parkinson's disease at the early stages in patients and animal models. J Clin Invest. 2022 Feb 15;132(4):e146400. doi: 10.1172/JCI146400.

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: May 17, 2022
• First Submitted That Met QC Criteria: May 17, 2022
• First Posted (Actual): May 23, 2022

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 38RC21.0421; 2022-A00337-36 (Other Identifier: ID RCB)

Drug and device information, study documents

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