Multicenter Study of Blood Biomarkers of Mitochondrial and Peroxisomal Metabolism to Differentiate Idiopathic Parkinson's Disease From Related Conditions

NCT05110547 | Unknown

• 1 other identifier: MOREAU 2020
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

With the aging of the population due to an increase in longevity, the number of people with Parkinson's disease is increasing (166,712 in France, as of December 31, 2015) and the number of patients with motor or cognitive-behavioral disorders is already a major public health challenge (1). In neurodegenerative diseases, the current strategy is to identify the disease early and, if possible, to consider therapeutic measures to slow down the progression of the disease. Classically, when faced with the early stages of Parkinsonism, the investigators differentiate idiopathic Parkinson's disease (IPD) from atypical Parkinsonian syndromes (AP), which include multiple system atrophy (MSA), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), for which the prognoses are more severe and the therapies less effective. In the early stage of the disease, when the symptoms are not do no yet differentiate the diseases, the differential diagnosis between IPD and PSP is a real challenge for clinicians (2). Cerebral MRI can help in the diagnosis but is most often only an indicator, as it may be normal in the early stages of the disease (2). The recent emergence of targeted therapies, specific to tauopathies or synucleinopathies, makes it essential to establish a diagnosis as early as possible in order to curb the evolution of the disease (3). The investigators propose here a first study on the analysis of biomarkers of neurodegeneration from lipid metabolism allowing to discriminate IPD and AP from peripheral blood. Two recent studies have provided evidence of the discriminatory character of neurofilament blood testing in the early phases of parkinsonism (4,5). On the other hand, to our knowledge, none of them has studied markers from mitochondrial and peroxisomal metabolism, which could play a key role in the pathophysiology of these diseases (6,7,8,9,10). Our strategy will therefore be to study idiopathic or atypical Parkinsonism subjects with a clearly established diagnosis in a cross-sectional manner, and to identify one or more blood markers of neurodegeneration predictive of IPD or AP, hypothesizing that these markers will be at significantly different levels between the two groups (descriptive analysis). The markers studied will include markers of neurodegeneration, markers of mitochondrial function, peroxisomal function and oxidative stress. The investigators will then study the correlations between these biomarkers and motor scores of disease severity.

Conditions

Idiopathic Parkinson Disease; Parkinsonian Syndrome

Outcome Measures

Primary Outcomes (8)

• Plasmatic measurement of 24S and 27 hydroxycholesterol

  Markers of neurodegeneration

  Baseline

• Plasmatic measurement on total leukocytes of the level of complexes 1 to 5 associated

  Markers of mitochondrial function

  Baseline

• Plasma assay of very long chain fatty acids

  Markers of peroxisomal function:

  Baseline

• Plasmatic measurement of ATP production

  Markers of mitochondrial function

  Baseline

• Plasma and leukocyte determination of Octanoyl Coenzyme A

  Markers reflecting the relationship between peroxisome and mitochondria:

  Baseline

• Dosage of uric acid

  Markers of oxidative stress

  Baseline

• Dosage of malondialdehyde (MDA)

  Markers of oxidative stress

  Baseline

• Plasmatic level of neurofilaments (SIMOA)

  Baseline

Study Arms (2)

Idiopathic Parkinson's disease

patients meeting the current clinical criteria whose disorders have progressed for strictly more than 2 years and strictly less than 7 years.

Biological: blood collection

atypical Parkinsonian syndromes

including the subgroups: multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration with a duration of disease progression strictly greater than 2 years and strictly less than 7 years, and meeting the current clinical criteria for each

Biological: blood collection

Interventions

blood collection BIOLOGICAL

2 additional 5ml EDTA tubes, with assays for the following markers: 24S and 27 hydroxycholesterol (gas chromatography-mass spectrometry, GC-MS), Neurofilaments (SIMOA), oxydative phosphorylation (OXPHOS) and quantitative measurement of intracellular ATP (ELISA), Very long chain fatty acids (GC-MS), Octanoyl CoA (HPLC), Uric acid, MDA assay (TBAR assay kit), and Lipid panel.

Idiopathic Parkinson's disease; atypical Parkinsonian syndromes

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients who regularly consult or are hospitalized at the Dijon University Hospital (in the Parkinson's disease unit) and at the Besancon University Hospital.

You may qualify if:

• For all patients:
• Age ≥ 18 years
• Patient affiliated to national health insurance
• Onset of symptoms strictly more than 2 years and less than 7 years ago
• Patient with a recent brain MRI to exclude patients with secondary parkinsonism (vascular parkinson,hydrocephalus at normal pressure)
• For patients in the "idiopathic Parkinson's disease group" :
• \- Idiopathic Parkinson's disease that is "possible," "probable," or "definite" according to UKPDSBB (UK Parkinson's Disease Society Brain Bank, Hughes et al. 1992) criteria.
• For patients in the "atypical parkinsonian syndrome" group:
• Subjects with a "possible" or "probable" diagnosis of MSA according to the diagnostic criteria of Gilman et al, 2008
• Or Subjects with a "possible" or "probable" diagnosis of AP according to the diagnostic criteria of Hoglinger et al, 2017
• Or Subjects with a "possible" or "probable" diagnosis of CBD according to the diagnostic criteria of Armstrong et al, 2013

You may not qualify if:

• For all patients:
• Disability making it impossible for him/her to participate in the trial due to lack of understanding of the information provided to him/her
• Patient under guardianship, curatorship or a measure of judicial protection
• Patients with any other neurological disease that could bias the results of our study: stroke, brain tumor, other neurodegenerative disease of the nervous system.
• Patients with secondary Parkinsonism (iatrogenic, toxic, inflammatory, post-traumatic)
• Patients with dyslipidemia receiving lipid-lowering treatment (statins, fibrates, inhibitors of intestinal cholesterol absorption).
• Patients with a progressive systemic disease that affects cholesterol metabolism, peroxisomal or mitochondrial function. (Examples: familial hypercholesterolemia, mitochondriopathy, peroxisome biogenesis disorders, etc.)
• Patient with a chronic disability making it impossible to collect clinical and cognitive data.
• Pregnant or breastfeeding women

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead

Study Sites (1)

Chu Dijon Bourgogne

Dijon, 21000, France

RECRUITING

MeSH Terms

Conditions

Parkinson Disease; Parkinsonian Disorders

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Thibault MOREAU

CONTACT

03 80 29 30 31; thibault.moreau@chu-dijon.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2021
• First Posted: November 8, 2021
• Study Start: April 27, 2021
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2023
• Last Updated: November 8, 2021

Record last verified: 2021-10

Locations

FR (1)