We aim to identify CSF and serum proteins in PD patients that are associated with disease progression and/or clinical phenotypic variations and serve to distinguish between PD and other Parkinsonian syndromes.
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
A lumbar puncture and a venous blood puncture will be performed in all patients
and controls. For the subsequent analysis of CSF and serum samples, we will use
a parallel approach. Previously discovered PD-related proteins will be
validated in CSF and blood samples of PD patients, patients with parkinsonian
symptoms not related to Parkinson*s disease and healthy controls using
enzyme-linked immunosorbent assays (ELISAs) and Western Blotting. For the PD
patients, we will analyze the association between CSF and serum proteins and
clinical characteristics. In addition, we will perform state-of-the-art
proteomics in order to discover new candidate biomarkers: proteins in CSF of
eight early-stage PD patients, eight moderately advanced cases, eight advanced
cases, and eight controls will be identified and quantified with stable isotope
labelling (iTRAQ) in conjunction with multidimensional liquid chromatography
coupled to tandem mass spectrometry. The newly discovered proteins will
subsequently be validated in both CSF and blood samples of PD patients with
various disease stages and clinical expression, patients with parkinsonian
syndromes and control patients to evaluate the specificity of sensitivity of
these potential biomarkers for PD, PD progression and PD phenotypes.
Secondary outcome
not applicable.
Background summary
Diagnosing Parkinson*s disease (PD), a disease affecting more than 4 million
people worldwide, can be very difficult in its early stages. Many other
parkinsonian syndromes, including vascular parkinsonism, progressive
supranuclear palsy (PSP) and multiple system atrophy (MSA), can mimic PD.
Cerebrospinal fluid (CSF) and serum proteins may serve as clinical biomarkers
and increase the accuracy of an early clinical diagnosis of PD. In addition,
they may enable us to monitor disease progression and give new insights into
molecular processes involved. The clinical expression and rate of progression
of is highly variable from one patient to another. Much is unknown about the
relation between the rate of progression and the clinical expression of PD.
Moreover, it is, yet unknown whether the clinical expression of PD is the
result of various sequential pathological processes in the peripheral and
central nervous system. Specific and sensitive biomarkers may give new insight
in the various clinical phenotypes and disease progression.
Study objective
We aim to identify CSF and serum proteins in PD patients that are associated
with disease progression and/or clinical phenotypic variations and serve to
distinguish between PD and other Parkinsonian syndromes.
Study design
cross-sectional.
Study burden and risks
For patients, procedures for the study will be combined with a regular visit to
the outpatient clinic for movement disorders. The procedures for this study for
newly presenting patients, i.e. venous blood puncture and lumbar puncture, will
take approximately 30 minutes. Patients already under treatment at the
outpatient clinic will be clinically characterized by means of questionnaires,
cognitive testing and clinical examination. These procedures will take 1,5
hours at the outpatient clinic and 2 hours at home to fill in the
questionnaires.
For controls, procedures consist of a general neurological examination,
cognitive testing, venous blood puncture and lumbar puncture with a total
duration of approximately 90 minutes.
Risks associated with venous blood puncture include haematomas and incidentally
infections. Risks associated with lumbar puncture include post lumbar puncture
headache, infection and haemorrhage. These risks will be minimized by the
applied puncture procedures.
De Boelelaan 1118
1081 HZ Amsterdam
NL
De Boelelaan 1118
1081 HZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
PATIENTS
(1) Patients of the outpatient clinic for movement disorders with a suspected parkinsonian syndrome, based upon the presence of at least one of the following parkinsonian symptoms: hypokinesia, bradykinesia, rigidity, tremor or postural instability.
(2) Patients already under treatment at the outpatient clinic for movement disorders and diagnosed with PD or one of the following other parkinsonian syndromes: MSA, PSP, vascular parkinsonism.
(3) Being able to understand the aim of the study and the study procedure and give written informed consent;HEALTHY CONTROLS
Being able to understand the aim of the study and the study procedure and give written informed consent
Exclusion criteria
PATIENTS
(1) A history of neurological disorders other than a parkinsonian syndrome, that affect the central nervous system or are known to influence CSF proteins
(2) Use of anticoagulants or indications for coagulation disorders
(3) Infected skin over the needle entry side for lumbar puncture
(4) Signs of raised intracranial pressure
(5) Unwillingness to be informed of unexpected medical findings;HEALTHY CONTROLS
(1) A history of neurological disorders that affect the central nervous system or are known to influence CSF proteins
(2) Abnormal findings at general neurological examination
(3) Use of anticoagulants or indications for coagulation disorders
(4) Infected skin over the needle entry side for lumbar puncture
(5) Signs of raised intracranial pressure
(6) Unwillingness to be informed of unexpected medical findings
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL23401.029.08 |