Biomarkers in Parkinsonian Syndromes

Recruiting

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

• Registration Number: NCT02114242
• Lead Sponsor: University Hospital, Bordeaux

Brief Summary

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.

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 Timeline

• Study Start: 2013-12-16
• Study First Submitted: 2014-02-06
• Study First Submitted QC: 2014-04-10
• Study First Posted: 2014-04-15
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-30
• Last Update Posted: 2022-03-31
• Primary Completion: 2023-12-16
• Study Completion: 2025-12-16

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Parkinson's disease patients	clinical measures of disease severity and progression	Patients suffering from Parkinson desease
progressive supranuclear palsy	CSF, blood and urine sampling	Patients suffering from progressive supranuclear palsy and age \> 40
multiple system atrophy patients	CSF, blood and urine sampling	Patients suffering from "probable" multiple system atrophy according to clinical consensus criteria and age \> 30
multiple system atrophy patients	clinical measures of disease severity and progression	Patients suffering from "probable" multiple system atrophy according to clinical consensus criteria and age \> 30
progressive supranuclear palsy	clinical measures of disease severity and progression	Patients suffering from progressive supranuclear palsy and age \> 40

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (3)

CHU de Limoges; 🇫🇷 Limoges, France

CHU de Bordeaux; 🇫🇷 Pessac, France

CHU de Toulouse; 🇫🇷 Toulouse, France