Biomarkers in Parkinsonian Syndromes (BIOPARK)

Development of Biomarkers for the Diagnosis and Prognosis of Parkinsonian Syndromes Running Head: Biomarkers in Parkinsonian Syndromes

Parkinson disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are neurodegenerative disorders. PD and MSA are alpha-synucleinopathies, which are characterized by the abnormal accumulation of alpha-synuclein, while tau protein accumulates in PSP. The development of biological markers for the diagnosis and prognosis in PD, MSA and PSP remains an unmet need. Such biological markers are crucial for future disease-modification and neuroprotection trials. Alpha-synuclein has a high potential for biomarker development since it constitutes the pathological hallmark feature in PD and MSA. The oligomeric alpha-synuclein seems to be particularly involved in abnormal protein aggregation in alpha-synucleinopathies.

The main objective is to compare oligomeric alpha-synuclein CSF levels between PD, MSA and PSP patients. PD and MSA patients will receive Cerebrospinal Fluid (CSF) and blood sampling at two study visits (baseline and after 12 months). Major secondary objectives are (i) to assess potential associations between the biomarker and clinical measures of disease severity and progression in MSA and PSP, and (ii) to assess the variation of the biomarker and its correlation to disease severity and progression in PD, MSA and PSP.

Study Overview

• Status: Recruiting
• Conditions: Parkinson's Disease; Multiple System Atrophy; Progressive Supranuclear Palsy; Parkinsonian Syndromes
• Intervention / Treatment: Other: clinical measures of disease severity and progression; Other: CSF, blood and urine sampling

Detailed Description

The differential diagnosis between Parkinson's disease, multiple system atrophy and progressive supranuclear palsy can be very difficult in early disease. PD, MSA and PSP are neurodegenerative disorders. PD and MSA belong to the alpha-synucleinopathies, which are characterized by the abnormal accumulation of alpha-synuclein. Alpha-synuclein accumulates in intraneuronal Lewy bodies in PD patients and as intracytoplasmic glial inclusions in MSA. In PSP, tau protein accumulates in neurons and glia cells while alpha-synuclein deposits are only found to a small extend.

The development of biological markers for the diagnosis and prognosis of PD, MSA and PSP remains an unmet need. Beyond guiding clinical decision-making, such biological markers are crucial for future disease-modification and neuroprotection trials.

Alpha-synuclein has a high potential for biomarker development since it constitutes the pathological hallmark feature of PD and MSA. The oligomeric alpha-synuclein fraction whose CSF levels are increased in PD seems to be particularly involved in abnormal protein aggregation in alpha-synucleinopathies.

The main objective of the study is to compare oligomeric alpha-synuclein CSF levels between PD, MSA and PSP patients. Secondary objectives are (i) to compare total alpha-synuclein levels and the index total/oligomeric alpha-synuclein between PD, MSA and PSP, (ii) to study the correlation and concordance between CSF and plasma levels of total and oligomeric alpha-synuclein, (iii) to assess potential associations between the biomarker and clinical measures of disease severity and progression and (iv) to assess the variation of the biomarker over time and its correlation to disease severity and progression.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Wassilios MEISSNER, Pr; Email: wassilios.meissner@chu-bordeaux.fr

Study Locations

• France
  • Limoges, France, 87000
    • Recruiting
    • CHU de Limoges
    • Contact: Frédéric Torny, MD
    • Principal Investigator: Frédéric Torny, MD
    • Sub-Investigator: Philippe Couratier, Pr
  • Pessac, France, 33640
    • Recruiting
    • CHU de Bordeaux
    • Contact: Wassilios MEISSNER, Pr
    • Principal Investigator: Wassilios MEISSNER, Pr
    • Sub-Investigator: François TISON, Pr
    • Sub-Investigator: Alexandra Foubert-Samier, MD
    • Sub-Investigator: Olivier Flabeau, Md
  • Toulouse, France, 31000
    • Not yet recruiting
    • CHU de Toulouse
    • Contact: Olivier RASCOL, Pr
    • Principal Investigator: Olivier RASCOL, PR
    • Sub-Investigator: Anne Pavy-Le Traon, MD
    • Sub-Investigator: Christine Brefel-Courbon, Dr
    • Sub-Investigator: Fabienne Ory-Magne, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients suffering from parkinson disease or multiple system atrophy or progressive supranuclear palsy.

Description

Patients receiving anticoagulants, showing abnormal coagulation on blood testing or thrombocytopenia are excluded from this study.

Patients showing more than 500 erythrocytes per mm3 of LCR are excluded from this study.

• PD patients

  • inclusion criteria:

    • Patients suffering from PD according to clinical criteria (Hughes et al, 1992)
    • Written informed consent
    • Patient covered by the national health system

  • exclusion criteria:

    • Patient under tutelage
    • patient covered by the national health system

• MSA patients

  • inclusion criteria:

    • Patients suffering from "possible" or "probable" MSA according to clinical consensus criteria (Gilman et al, 2008), age > 30
    • Written informed consent
    • Patient covered by the national health system

  • exclusion criteria:

    • UMSARS IV score >4 points
    • Patient under tutelage

• PSP patients

  • inclusion criteria:

    • Patients suffering from PSP according to NNIPPS trial criteria (Bensimon et al., 2009), age > 40
    • Written informed consent
    • Patient covered by the national health system

  • exclusion criteria:

    • PSPRS item 26 score >3 points
    • Patient under tutelage

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Parkinson's disease patients; Patients suffering from Parkinson desease	Other: clinical measures of disease severity and progression; Questionnaires (quality of life, motricity scales, cognitive scales, depression scales, scale of sleep quality)
multiple system atrophy patients; Patients suffering from "probable" multiple system atrophy according to clinical consensus criteria and age > 30	Other: clinical measures of disease severity and progression; Questionnaires (quality of life, motricity scales, cognitive scales, depression scales, scale of sleep quality); Other: CSF, blood and urine sampling; PSP and MSA patients will receive CSF and blood sampling at two study visits (baseline and after 12 months).
progressive supranuclear palsy; Patients suffering from progressive supranuclear palsy and age > 40	Other: clinical measures of disease severity and progression; Questionnaires (quality of life, motricity scales, cognitive scales, depression scales, scale of sleep quality); Other: CSF, blood and urine sampling; PSP and MSA patients will receive CSF and blood sampling at two study visits (baseline and after 12 months).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Concentration of oligomeric alpha-synuclein in cerebrospinal fluid	at day 0 (inclusion) and one year after inclusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Total alpha-synuclein concentration in CSF, oligomeric/total alpha-synuclein ratio in CSF	At inclusion (Day 0) and one year after inclusion
Oligomeric and total alpha-synuclein concentration in plasma, oligomeric/total alpha-synuclein ratio in plasma	At inclusion (Day 0) and one year after inclusion
Alpha-synuclein levels in relation to disease severity and progression, disease duration and age	At inclusion (Day 0) and one year after inclusion
Variation of alpha-synuclein levels between first and second sampling	At inclusion (Day 0) and one year after inclusion

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Study Chair: Rodolphe THIEBAUT, MD, University Hospital, Bordeaux; Principal Investigator: Wassilios MEISSNER, Pr, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2013
• Primary Completion (Anticipated): December 16, 2023
• Study Completion (Anticipated): December 16, 2025

Study Registration Dates

• First Submitted: February 6, 2014
• First Submitted That Met QC Criteria: April 10, 2014
• First Posted (Estimate): April 15, 2014

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 30, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Parkinson's disease; multiple system atrophy; progressive supranuclear palsy; alpha-synuclein
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Disease; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Pathological Conditions, Anatomical; Tauopathies; Cranial Nerve Diseases; Autonomic Nervous System Diseases; Ocular Motility Disorders; Paralysis; Primary Dysautonomias; Hypotension; Ophthalmoplegia; Syndrome; Parkinson Disease; Atrophy; Multiple System Atrophy; Shy-Drager Syndrome; Parkinsonian Disorders; Supranuclear Palsy, Progressive
• Other Study ID Numbers: CHUBX 2012/27