GLIAPARK: Identification of a Biomarker Predictive of Evolution of Parkinson Disease

Sponsor
Nantes University Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT03230526
Collaborator
(none)
64
4
78
16
0.2

Study Details

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
  • 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
Anticipated 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 :
Apr 16, 2018
Anticipated Primary Completion Date :
Oct 16, 2024
Anticipated Study Completion Date :
Oct 16, 2024

Outcome Measures

Primary Outcome Measures

  1. Coefficient of correlation between level of microglial striatal activation and the And the dopaminergic denervation kinetics [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 [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [baseline]

    QUIP RS

  12. Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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 [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 [36 Months]

    QUIP questionnaire

  58. Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57 [36 Months]

    NMS questionnaire

  59. Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57 [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 [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) [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. [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. [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. [36 months]

    Neurologic Evaluation

  65. Evaluate the link between the level of nigrostriatal microglial activation and the serum level of biological markers of inflammation [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 [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 [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 [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 [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 [36 months]

    Measurement of serum uric acid

Eligibility Criteria

Criteria

Ages Eligible for Study:
40 Years to 67 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Locations

Site City State Country Postal Code
1 CHU de Nantes Nantes France
2 Centre Eugène Marquis Rennes France
3 CHU de Rennes Rennes France
4 CHU de Tours Tours France

Sponsors and Collaborators

  • Nantes University Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Nantes University Hospital
ClinicalTrials.gov Identifier:
NCT03230526
Other Study ID Numbers:
  • RC17_0012
  • 2017-000411-16
First Posted:
Jul 26, 2017
Last Update Posted:
Sep 20, 2021
Last Verified:
Sep 1, 2021
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 20, 2021