Identification of a Biomarker Predictive of Evolution of Parkinson Disease (GLIAPARK)

Brain Microglial Activation in the Early Stage of the Parkinson's Disease: a Predictive Biomarker of the Evolution?

Phase II, Open-labeled, Prospective, Multi-center study of assessing the link between microglial activation and dopaminergic denervation kinetics in the early stage of Parkinson disease, by using the imaging of [18F]DPA-714 a new ligand of Translocator Protein-18 kDa (TSPO) by Positron Emission Tomography (PET).

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: [18F]DPA-714 PET scan

Detailed Description

The Parkinson's disease ( MP) is a frequent but heterogeneous neurodegenerative disease in term of clinical presentation(display) and evolutionary profile. The therapeutic coverage(care) of the patients would thus be personalized Such an approach remains still in its infancy in 2017. Better know the factors which determine the evolutionary clinical subcategories is a major question of the current researches on the Parkinson disease. Nigrostriaial inflammation is an interesting candidate. Microglia activation is closely associated with the degenerative process.

Development of the molecular imaging allows to study nigrostriatal inflammation in vivo in human by positron emission tomography (PET) by using the radiotracer of the protein of translocation of 18KDa ( TSPO), considered as a marker of microglia activation Some studies showed an increase of the inflammation in the striatum and in the substantia nigra, the sites of the dopaminergic degeneration (The lesional core of the Parkinson disease is the damage of the dopaminergic nigrostriatale way). However data remain rare and concern small number of patients. Some data are inconsistent because of problems of specificity of the ligands used and variation between populations of studied patients (duration of disease evolution).

In this study, investigators suggest studying by imaging TEP using a ligand new of the TSPO, [18F]DPA-714, microglial brain activation in the early stage of the Parkinson disease and determine wether it is predictive of speed of disease progression.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Nantes, France
    • Chu De Nantes
  • Rennes, France
    • Centre Eugène Marquis
  • Rennes, France
    • CHU de Rennes
  • Tours, France
    • CHU de Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 67 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients having a Parkinson's disease diagnosed according to the criteria UKPDSBB.
• Diagnosis done less than three years before the date the inclusion.
• Patient Age at diagnosis : between 40 and 65 years.
• Absence of clinical arguments for an associated neurovascular pathology.
• Written consent obtained.
• HAB polymorphism in the genotyping of TSPO gene.
• Brain MRI without following abnormalities: cortical or sub-cortical atrophy or hippocampal atrophy (Scheltens score ≥2), vascular encephalopathy (Fazekas score > 2, > 10 microbleed) or showing signs in favour of atypical parkinson syndrome.

Exclusion Criteria:

• Pregnant woman
• Minor
• Adult protected by the law
• Contraindication to PET-scan
• Contraindication to brain MRI
• History of inflammatory or dysimmune chronic disease
• History of psychiatric disease or drug addiction
• History of cognitive disorders (MMS<26)
• Hypersensibility to iodine derivates or one of these components
• Long-term Treatments which can interfere in neuroinflammation process
• Treatments / substances susceptible to interfere with the 18F-DPA-714
• TSPO gene Polymorphisms rs6971 corresponding to groups of affinity of low affinity (LAB=Low Affinity Binder) or moderated MAB = Mixed Affinity Binder)
• Modification of diagnosis of Parkinson disease during follow-up, in particular towards an atypical parkinson-like syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coefficient of correlation between level of microglial striatal activation and the And the dopaminergic denervation kinetics	Coefficient of correlation between the striatal microglial activation level measured by PET imaging [binding potential (BP) of 18F-DPA-714 in the striatum] and dopaminergic denervation kinetics obtained from two 123I-FP-CIT (DaTscan) scans	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)	The equivalent dose of cumulative L-Dopa	baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)	The equivalent dose of cumulative L-Dopa	18 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)	MDS-UPDRS scale (part III "OFF" - Part III "ON" and part II)	Baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)	MDS-UPDRS scale (part III "OFF" - Part III "ON" and part II)	18 Months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)	MDS-UPDRS scale (part IV)	baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)	MDS-UPDRS scale (part IV)	18 months
Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors)	QUIP RS	baseline
Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors)	QUIP RS	18 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)	MDS-UPDRS scale (part III ON : 3.1 ; 3.2 ; 3.9 to 3.13)	baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)	MDS-UPDRS scale (part III ON : 3.1 ; 3.2 ; 3.9 to 3.13)	18 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)	MDS-UPDRS scale (part II : 2.13 and part III : 3.11)	baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)	MDS-UPDRS scale (part II : 2.13 and part III : 3.11)	18 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	MDS-UPDRS scale (part I)	Baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	MDS-UPDRS scale (part I)	18 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	NMS SCALE	baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	NMS SCALE	18 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Scopa-Aut Score	baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Scopa-Aut Score	18 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Evaluation of constipation according to Rome III criteria	Baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Evaluation of constipation according to Rome III criteria	18 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Detection of hypotension	Baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Detection of hypotension	18 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Detection of paradoxical sleep disorder, according to the questionnaire for the detection of REM sleep disorders	Baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Detection of paradoxical sleep disorder, according to the questionnaire for the detection of REM sleep disorders	18 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Epworth's Sleepiness Scale	Baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Epworth's Sleepiness Scale	18 Months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	UPSIT test	baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	MoCA score	Baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	MoCA score	18 Months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	MATTIS scale	Baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	MATTIS scale	18 Months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Anxiety symptoms assessed using Beck's anxiety inventory	Baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Anxiety symptoms assessed using Beck's anxiety inventory	18 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Symptoms of depression assessed using the Beck Depression	Baseline
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Symptoms of depression assessed using the Beck Depression	18 Months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic denervation at baseline (DaTscan initial)	Dopaminergic denervation at inclusion will be measured by the binding potential (BP) of ioflupane (123I-FP-CIT) by regions of interest in the caudate and putamen of the striatum	Baseline
Assess the relationship between the level of microglial activation in the extra-striatal cortical (cortex and brain stem) regions and the presence of non-motor and axial motor symptoms.	Neurologic Evaluation	baseline
Assess the relationship between the level of microglial activation in the extra-striatal cortical (cortex and brain stem) regions and the presence of non-motor and axial motor symptoms.	Neurologic Evaluation	18 months
Evaluate the link between the level of nigrostriatal microglial activation and the serum level of biological markers of inflammation	The serum levels of 13 cytokines will be analyzed	Baseline
Evaluate the link between the level of nigrostriatal microglial activation and the serum level of biological markers of inflammation Evaluate the relationship between the level of nigrostriatal microglial activation	The serum levels of 13 cytokines will be analyzed	18 months
Evaluate the relationship between the level of nigrostriatal microglial activation and the serum uric acid level at 0, 18 and 36 months	Measurement of serum uric acid	Baseline
Evaluate the relationship between the level of nigrostriatal microglial activation and the serum uric acid level at 0, 18 and 36 months	Measurement of serum uric acid	18 months
Analyze the relationship between the level of microglial activation in the black substance at the early stage of MP and the dopaminergic denervation kinetics	Will be estimated by imaging PET with [18F]DPA-714	24 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)	The equivalent dose of cumulative L-Dopa	24 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)	MDS-UPDRS scale (part III "OFF" - Part III "ON" and part II)	24 Months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)	MDS-UPDRS scale (part IV)	24 months
Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors)	QUIP RS	24 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)	MDS-UPDRS scale (part III ON : 3.1 ; 3.2 ; 3.9 to 3.13)	24 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)	MDS-UPDRS scale (part II : 2.13 and part III : 3.11)	24 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	MDS-UPDRS scale (part I)	24 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	NMS SCALE	24 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Scopa-Aut Score	24 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Evaluation of constipation according to Rome III criteria	24 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Detection of hypotension	24 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Detection of paradoxical sleep disorder, according to the questionnaire for the detection of REM sleep disorders	24 months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Epworth's Sleepiness Scale	24 Months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	UPSIT test	24 Months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	MoCA score	24 Months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	MATTIS scale	24 Months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Anxiety symptoms assessed using Beck's anxiety inventory	24 Months
Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)	Symptoms of depression assessed using the Beck Depression	24 Months
Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57	MDS-UPDRS scale	24 Months
Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57	QUIP questionnaire	24 Months
Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57	NMS questionnaire	24 Months
Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57	Scopa-Aut Score	24 Months
Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57	Rome III criteria	24 Months
Evaluate the link between the level of striatal microglial activation and the level of activation in other brain regions (black substance, bridge and cortex)	The level of cortical microglial activation measured by fixation of the radioligand 18F-DPA-714, on some volumes of interest in the brain	24 months
Assess the relationship between the level of microglial activation in the extra-striatal cortical (cortex and brain stem) regions and the presence of non-motor and axial motor symptoms.	Neurologic Evaluation	24 months
Evaluate the link between the level of nigrostriatal microglial activation and the serum level of biological markers of inflammation	The serum levels of 13 cytokines will be analyzed	24 months
Evaluate the relationship between the level of nigrostriatal microglial activation and the serum uric acid level at 0, 18 and 36 months	Measurement of serum uric acid	24 months

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2018
• Primary Completion (Estimated): May 6, 2024
• Study Completion (Estimated): May 6, 2024

Study Registration Dates

• First Submitted: July 18, 2017
• First Submitted That Met QC Criteria: July 25, 2017
• First Posted (Actual): July 26, 2017

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: RC17_0012; 2017-000411-16 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No