Measure of Microglial Activation in the Brain of Parkinson Disease Patients With PET

NCT02319382 | Unknown DMC

• 1 other identifier: P091202
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson's Disease With LRRK2 Mutation; Healthy Controls; Parkinson's Disease Without LRRK2 Mutation

Keywords

Parkinson Disease; [18F]DPA-714; Positron emission tomography (PET); Neuroinflammation

Outcome Measures

Primary Outcomes (1)

• Accumulation of [18F]DPA-714 in the midbrain assessed through PET

  Inclusion visit

Study Arms (1)

2 markers: 18F-DPA-714 and 11C-PE2I

EXPERIMENTAL

PET with the tracer \[18F\]DPA-714 and second PET with the tracer \[11C\]-PE2I. \[18F\]DPA-714 is a new marker. It allows the macroscopic visualization of active microglia in the brain. \[11C\]-PE2I allow measures dopaminergic neuronal loss.

Radiation: PET with the tracer 18F-DPA-714; Radiation: PET with the tracer 11C-PE2I; Other: MRI

Interventions

PET with the tracer 18F-DPA-714 RADIATION

2 markers: 18F-DPA-714 and 11C-PE2I

PET with the tracer 11C-PE2I RADIATION

2 markers: 18F-DPA-714 and 11C-PE2I

MRI OTHER

Magnetic field

2 markers: 18F-DPA-714 and 11C-PE2I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Group 1:
• Parkinson disease diagnosed for less than 18 months and no treatment Age at disease over 40 years
• Group 2:
• 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
• Group 3:
• 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 )
• Group 4:
• Parkinson disease LRRK2 mutation proved by genetic analysis
• Group 5:
• 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
• Group 6:
• No evidence of Parkinson disease attested by a UPDRS score of 0 or1

You may not qualify if:

• 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:
• Group 1:
• Atypical parkinsonism Other neurological diseases or known brain lesion
• Group 2:
• Atypical parkinsonian syndrome
• Group 3:
• 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
• Group 6:
• Previous neurological or psychiatry diseases or known brain lesion

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• France Parkinson Association: collaborator

Study Sites (1)

Orsay Hospital

Orsay, 91401, France

RECRUITING

Related Publications (3)

• Peyronneau MA, Kuhnast B, Nguyen DL, Jego B, Sayet G, Caille F, Lavisse S, Gervais P, Stankoff B, Sarazin M, Remy P, Bouilleret V, Leroy C, Bottlaender M. [18F]DPA-714: Effect of co-medications, age, sex, BMI and TSPO polymorphism on the human plasma input function. Eur J Nucl Med Mol Imaging. 2023 Sep;50(11):3251-3264. doi: 10.1007/s00259-023-06286-1. Epub 2023 Jun 9.

  PMID: 37291448 DERIVED

• Ricigliano VAG, Louapre C, Poirion E, Colombi A, Yazdan Panah A, Lazzarotto A, Morena E, Martin E, Bottlaender M, Bodini B, Seilhean D, Stankoff B. Imaging Characteristics of Choroid Plexuses in Presymptomatic Multiple Sclerosis: A Retrospective Study. Neurol Neuroimmunol Neuroinflamm. 2022 Oct 13;9(6):e200026. doi: 10.1212/NXI.0000000000200026. Print 2022 Nov.

  PMID: 36229188 DERIVED

• Lavisse S, Goutal S, Wimberley C, Tonietto M, Bottlaender M, Gervais P, Kuhnast B, Peyronneau MA, Barret O, Lagarde J, Sarazin M, Hantraye P, Thiriez C, Remy P. Increased microglial activation in patients with Parkinson disease using [18F]-DPA714 TSPO PET imaging. Parkinsonism Relat Disord. 2021 Jan;82:29-36. doi: 10.1016/j.parkreldis.2020.11.011. Epub 2020 Nov 17.

  PMID: 33242662 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Neuroinflammatory Diseases

Interventions

2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Philippe REMY, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Philippe REMY, MD, PhD

CONTACT

(0)1.69.86.77.27; neuro-philippe.remy@hmn.aphp.fr

Sonia LAVISSE, PhD

CONTACT

(0)1.69.86.78.91; sonia.lavisse@cea.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2014
• First Posted: December 18, 2014
• Study Start: June 1, 2012
• Primary Completion: November 1, 2016
• Study Completion: December 1, 2016
• Last Updated: July 14, 2015

Record last verified: 2015-07

Locations

FR (1)