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

• ClinicalTrials.gov Identifier: NCT03230526
• Recruitment Status: Recruiting
• First Posted: July 26, 2017
• Last Update Posted: September 20, 2021
• Sponsor: Nantes University Hospital
• Information provided by (Responsible Party): Nantes University Hospital

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Parkinson Disease	Drug: [18F]DPA-714 PET scan	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 64 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Brain Microglial Activation in the Early Stage of the Parkinson's Disease: a Predictive Biomarker of the Evolution?
• Actual Study Start Date: April 16, 2018
• Estimated Primary Completion Date: October 16, 2024
• Estimated Study Completion Date: October 16, 2024

Arms and Interventions

Intervention Details:

• Drug: [18F]DPA-714 PET scan

  One PET scan using [18F]DPA-714 is done at M2 between two [123I]FP-CIT scan (DaTscan) done at M1 and M35.

  Neuropsychological assessment is done at M0, M18 and M36

Outcome Measures

Primary Outcome Measures :

1. Coefficient of correlation between level of microglial striatal activation and the And the dopaminergic denervation kinetics [ Time Frame: 36 months ]
   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

Secondary Outcome Measures :

1. Analyze the relationship between the level of microglial activation in the black substance at the early stage of MP and the dopaminergic denervation kinetics [ Time Frame: 36 months ]
   Will be estimated by imaging PET with [18F]DPA-714
2. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors) [ Time Frame: baseline ]
   The equivalent dose of cumulative L-Dopa
3. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors) [ Time Frame: 18 months ]
   The equivalent dose of cumulative L-Dopa
4. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors) [ Time Frame: 36 months ]
   The equivalent dose of cumulative L-Dopa
5. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors) [ Time Frame: Baseline ]
   MDS-UPDRS scale (part III "OFF" - Part III "ON" and part II)
6. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors) [ Time Frame: 18 Months ]
   MDS-UPDRS scale (part III "OFF" - Part III "ON" and part II)
7. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors) [ Time Frame: 36 Months ]
   MDS-UPDRS scale (part III "OFF" - Part III "ON" and part II)
8. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors) [ Time Frame: baseline ]
   MDS-UPDRS scale (part IV)
9. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors) [ Time Frame: 18 months ]
   MDS-UPDRS scale (part IV)
10. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors) [ Time Frame: 36 months ]
    MDS-UPDRS scale (part IV)
11. Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors) [ Time Frame: baseline ]
    QUIP RS
12. Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors) [ Time Frame: 18 months ]
    QUIP RS
13. Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors) [ Time Frame: 36 months ]
    QUIP RS
14. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor) [ Time Frame: baseline ]
    MDS-UPDRS scale (part III ON : 3.1 ; 3.2 ; 3.9 to 3.13)
15. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor) [ Time Frame: 18 months ]
    MDS-UPDRS scale (part III ON : 3.1 ; 3.2 ; 3.9 to 3.13)
16. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor) [ Time Frame: 36 months ]
    MDS-UPDRS scale (part III ON : 3.1 ; 3.2 ; 3.9 to 3.13)
17. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor) [ Time Frame: baseline ]
    MDS-UPDRS scale (part II : 2.13 and part III : 3.11)
18. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor) [ Time Frame: 18 months ]
    MDS-UPDRS scale (part II : 2.13 and part III : 3.11)
19. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor) [ Time Frame: 36 months ]
    MDS-UPDRS scale (part II : 2.13 and part III : 3.11)
20. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: Baseline ]
    MDS-UPDRS scale (part I)
21. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 18 months ]
    MDS-UPDRS scale (part I)
22. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 36 months ]
    MDS-UPDRS scale (part I)
23. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: baseline ]
    NMS SCALE
24. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 18 months ]
    NMS SCALE
25. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 36 months ]
    NMS SCALE
26. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: baseline ]
    Scopa-Aut Score
27. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 18 months ]
    Scopa-Aut Score
28. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 36 months ]
    Scopa-Aut Score
29. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: Baseline ]
    Evaluation of constipation according to Rome III criteria
30. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 18 months ]
    Evaluation of constipation according to Rome III criteria
31. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 36 months ]
    Evaluation of constipation according to Rome III criteria
32. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: Baseline ]
    Detection of hypotension
33. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 18 months ]
    Detection of hypotension
34. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 36 months ]
    Detection of hypotension
35. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: Baseline ]
    Detection of paradoxical sleep disorder, according to the questionnaire for the detection of REM sleep disorders
36. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 18 months ]
    Detection of paradoxical sleep disorder, according to the questionnaire for the detection of REM sleep disorders
37. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 36 months ]
    Detection of paradoxical sleep disorder, according to the questionnaire for the detection of REM sleep disorders
38. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: Baseline ]
    Epworth's Sleepiness Scale
39. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 18 Months ]
    Epworth's Sleepiness Scale
40. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 36 Months ]
    Epworth's Sleepiness Scale
41. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: baseline ]
    UPSIT test
42. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 36 Months ]
    UPSIT test
43. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: Baseline ]
    MoCA score
44. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 18 Months ]
    MoCA score
45. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 36 Months ]
    MoCA score
46. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: Baseline ]
    MATTIS scale
47. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 18 Months ]
    MATTIS scale
48. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 36 Months ]
    MATTIS scale
49. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: Baseline ]
    Anxiety symptoms assessed using Beck's anxiety inventory
50. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 18 months ]
    Anxiety symptoms assessed using Beck's anxiety inventory
51. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 36 Months ]
    Anxiety symptoms assessed using Beck's anxiety inventory
52. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: Baseline ]
    Symptoms of depression assessed using the Beck Depression
53. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 18 Months ]
    Symptoms of depression assessed using the Beck Depression
54. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor) [ Time Frame: 36 Months ]
    Symptoms of depression assessed using the Beck Depression
55. Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic denervation at baseline (DaTscan initial) [ Time Frame: Baseline ]
    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
56. Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57 [ Time Frame: 36 Months ]
    MDS-UPDRS scale
57. Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57 [ Time Frame: 36 Months ]
    QUIP questionnaire
58. Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57 [ Time Frame: 36 Months ]
    NMS questionnaire
59. Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57 [ Time Frame: 36 Months ]
    Scopa-Aut Score
60. Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57 [ Time Frame: 36 Months ]
    Rome III criteria
61. Evaluate the link between the level of striatal microglial activation and the level of activation in other brain regions (black substance, bridge and cortex) [ Time Frame: 36 months ]
    The level of cortical microglial activation measured by fixation of the radioligand 18F-DPA-714, on some volumes of interest in the brain
62. 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. [ Time Frame: baseline ]
    Neurologic Evaluation
63. 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. [ Time Frame: 18 months ]
    Neurologic Evaluation
64. 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. [ Time Frame: 36 months ]
    Neurologic Evaluation
65. Evaluate the link between the level of nigrostriatal microglial activation and the serum level of biological markers of inflammation [ Time Frame: Baseline ]
    The serum levels of 13 cytokines will be analyzed
66. 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 [ Time Frame: 18 months ]
    The serum levels of 13 cytokines will be analyzed
67. Evaluate the link between the level of nigrostriatal microglial activation and the serum level of biological markers of inflammation [ Time Frame: 36 months ]
    The serum levels of 13 cytokines will be analyzed
68. Evaluate the relationship between the level of nigrostriatal microglial activation and the serum uric acid level at 0, 18 and 36 months [ Time Frame: Baseline ]
    Measurement of serum uric acid
69. Evaluate the relationship between the level of nigrostriatal microglial activation and the serum uric acid level at 0, 18 and 36 months [ Time Frame: 18 months ]
    Measurement of serum uric acid
70. Evaluate the relationship between the level of nigrostriatal microglial activation and the serum uric acid level at 0, 18 and 36 months [ Time Frame: 36 months ]
    Measurement of serum uric acid

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Anne-Gaëlle CORBILLE, MD; +33240165212; anne-gaelle.corbille@chu-nantes.fr

Contact: Evelyne SCOTET-CERATO, PhD; +33253482840; evelyne.cerato@chu-nantes.fr

Locations

France

CHU de Nantes; Recruiting

Nantes, France

Contact: Anne Gaëlle Corbille

Principal Investigator: Anne Gaëlle Corbille

Centre Eugène Marquis; Not yet recruiting

Rennes, France

Contact: Florence Lejeune

Principal Investigator: Florence Lejeune

CHU de Rennes; Not yet recruiting

Rennes, France

Contact: Marc Verin

Principal Investigator: Marc Verin

CHU de Tours; Recruiting

Tours, France

Contact: Jean-Luc HOUETO

Principal Investigator: Jean-Luc HOUETO

Sponsors and Collaborators

Nantes University Hospital

More Information

• Responsible Party: Nantes University Hospital
• ClinicalTrials.gov Identifier: NCT03230526
• Other Study ID Numbers: RC17_0012; 2017-000411-16 ( EudraCT Number )
• First Posted: July 26, 2017
• Last Update Posted: September 20, 2021
• Last Verified: September 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

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