Brief Title
Biomarkers in Parkinsonian Syndromes
Official Title
Development of Biomarkers for the Diagnosis and Prognosis of Parkinsonian Syndromes Running Head: Biomarkers in Parkinsonian Syndromes
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 Type
Observational
Primary Outcome
Concentration of oligomeric alpha-synuclein in cerebrospinal fluid
Secondary Outcome
Total alpha-synuclein concentration in CSF, oligomeric/total alpha-synuclein ratio in CSF
Condition
Parkinsonian Syndromes
Intervention
CSF, blood and urine sampling
Study Arms / Comparison Groups
Parkinson's disease patients
Description: Patients suffering from Parkinson desease
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Other
Estimated Enrollment
100
Start Date
December 16, 2013
Completion Date
December 16, 2023
Primary Completion Date
December 16, 2021
Eligibility Criteria
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Wassilios MEISSNER, Pr, , [email protected]
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT02114242
Organization ID
CHUBX 2012/27
Responsible Party
Sponsor
Study Sponsor
University Hospital, Bordeaux
Study Sponsor
Wassilios MEISSNER, Pr, Principal Investigator, University Hospital, Bordeaux
Verification Date
April 2020