High Resolution PET Imaging of Microglial Activation in Parkinson's Disease (PD) With a New Tracer [18F]DPA-714
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Parkinson's Disease With LRRK2 Mutation
- Sponsor
- Assistance Publique - Hôpitaux de Paris
- Enrollment
- 46
- Locations
- 1
- Primary Endpoint
- Accumulation of [18F]DPA-714 in the midbrain assessed through PET
- Last Updated
- 10 years ago
Overview
Brief Summary
There is accumulating evidence suggesting that inflammatory processes, through microglial activation, would play a key role in the neurodegenerative process of Parkinson's disease (PD). It is considered that microglial activation would be part of self-propelling cycle of neuroinflammation that fuels the progressive dopaminergic neurodegeneration. It is however hard to evidence microglial activation in vivo, especially in the substantia nigra: first, the investigators need very high resolution imaging tools and then, the only ligand available to date, 11C-PK11195, has a low sensitivity and specificity and provided heterogeneous results.
18F-DPA-714 is a new PET ligand which labels microglial cells. The investigators aim to explore the topography and intensity of microglial activation in several different groups of PD patients: 1) de novo, drug-naïve subjects (n = 6); 2) non-fluctuating treated patients ("honeymoon") (n = 10); 3) advanced drug-responsive patients motor fluctuations (wearing-off or dyskinesia) (n = 6); 4) patients with LRRK2 gene mutation (n = 6); and 5) related to healthy patients carriers of the mutation LRRK2(n = 6). PET imaging will be performed with a new generation tomography having a very high resolution.
This study might reveal significant neuroinflammatory process in the midbrain of PD patients and will determine if such process is present in both sporadic and genetic forms of PD. The results of this study might provide a new biomarker of disease pathological progression and help as identifying subjects who might most benefit from a specific anti-inflammatory drug.
Investigators
Eligibility Criteria
Inclusion Criteria
- •For all subjects:
- •The subject is an out-patient aged 18 years or above Active affiliation to national health insurance system Signed informed consent to participate in the study
- •Additional criteria depending on the group under study:
- •Parkinson disease diagnosed for less than 18 months and no treatment Age at disease over 40 years
- •Disease Parkinson diagnosed for less than 36 months and treated by L-Dopa or /and dopaminergic agonist No motor fluctuation Age at disease over 40 years
- •Parkinson disease diagnosed for more than 3 years Age at disease over 40 years Motor fluctuations for more than 6 months (dyskinesia or wearing off )
- •Parkinson disease LRRK2 mutation proved by genetic analysis
- •LRRK2 mutation proved by genetic analysis No evidence of Parkinson disease attested by a Unified Parkinson's Disease Rating Scale (UPDRS) score of 0 or1
- •No evidence of Parkinson disease attested by a UPDRS score of 0 or1
Exclusion Criteria
- •For all subjects:
- •Contraindication for MRI Anti-inflammation treatment for more 50 days during previous year or for more 7 days during previous month Pregnancy or lactating Legal incapacity or limited legal capacity Beneficiary of AME
- •Additional criteria depending on the group under study:
- •Atypical parkinsonism Other neurological diseases or known brain lesion
- •Atypical parkinsonian syndrome
- •Atypical parkinsonian syndrome Resistance to treatment (benefit of treatment estimated to less than 30%) Other neurological diseases or known brain lesion
- •Groups 4 and 5:
- •Other neurological diseases or known brain lesion
- •Previous neurological or psychiatry diseases or known brain lesion
Outcomes
Primary Outcomes
Accumulation of [18F]DPA-714 in the midbrain assessed through PET
Time Frame: Inclusion visit