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Completed

NCT Number: NCT03918616

P2X7 Receptor, Inflammation and Neurodegenerative Diseases

Parkinson disease (PD) is a chronic degenerative disease characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Its pathophysiological mechanisms are still partially unknown; a main role seems to be played by chronic neuroinflammation. A few reports have addressed the possible involvement of the inflammasome in PD, just describing the protective effect of P2X7 purinergic receptor (P2X7R) blockers in murine models of the disease and in microglial cells, where NLRP3 is activated by α-Synuclein, triggering a neuroinflammation that contributes to degeneration of dopaminergic neurons. It is still unclear whether, in addition to the increased brain expression and function of the nucleotide-binding domain, leucine-rich repeat, pyrin domain containing type 3 (NLRP3) inflammasome platform, a systemic activation of such complex might participate in the pathogenesis of PD, which could be the role of the P2X7R in this scenario, and whether such patterns undergo any specific epigenetic regulation. The present study has been designed to address these issues.

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Key information

Conditions

Neuro-Degenerative Disease Alzheimer Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Dementia Mental Disorders Movement Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Parkinson Disease Parkinsonian Disorders Synucleinopathies Tauopathies

Age range

45 year–80 year

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Pisa

Pisa, 56125, Italy

About this study

The day of the study patientes underwent a complete clinical evaluation and assessment of psycho-physical abilities using specific test such as Mini-Mental State Examination (MMSE), Cognitive Alzheimer's Disease Assessment Scale (ADAS-Cog), Clinical Dementia Rating Scale, Unified Parkinson's Disease Rating Scale (UPDRS). Blood samples were collected from an antecubital vein to assess serum and plasma aliquots for blood routine analysis and RNA and protein extraction from circulating lymphomonocytes.

To explore a putative epigenetic regulation of such complex scenario some circulating miRNAs likely involved in the pathogenesis of neurological diseases and neuro-inflammation will be measured.

Expression and functional activity of P2X7R-inflammasome complex will be measured by PCR and WB. Acute phase cytokines inflammasome-related levels will be determined by ELISA. Biochemical parameters (fasting glucose, lipid profile, serum creatinine, uric acid) will be measured by standard methods in the biochemistry laboratory of the University Hospital in Pisa. The same determinations will be repeated after one year from the first visit.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • newly-diagnosed PD or AD;
  • no previous specific treatment;
  • no systemic inflammatory or immunological disease and/or cancer;
  • no anti-inflammatory drugs assumed in the three months preceding the enrolment;
  • patients able to consent.

Exclusion criteria

  • history of strokes or any neurological disease;
  • patients assuming neuroleptic drugs;
  • atypical symptoms at onset.

Treatment and study plan

Memantine, Dopamine receptor-agonists

Drug

The study do not provide any experimental drugs. Patientes will receive treatment routinary used by Neurologist for these diseases.

Other names: Memantine: Ebixa. Dopamine receptor-agonists: Sinemet, Sirio.

Primary outcomes

  1. Change from baseline in P2X7R-inflammasome activity

    Time frame: each patient will be assessed one year after diagnosis

    NLRP3-ASC-Caspase-1 activity is measured using RT-PCR

  2. Change from baseline in NFkB activity

    Time frame: each patient will be assessed one year after diagnosis

    NFkB activity is measured using RT-PCR

  3. Change from baseline in serum α-synuclein

    Time frame: each patient will be assessed one year after diagnosis

    Circulating levels of α-synuclein are determined using high sensitivity Quantikine enzyme-linked immunosorbent assay (ELISA) and express as [ng/ml]

  4. Change from baseline in serum IL-1β

    Time frame: each patient will be assessed one year after diagnosis

    Circulating levels of IL-1β are determined using high sensitivity Quantikine enzyme-linked immunosorbent assay (ELISA) and express as [pg/ml]

  5. Change from baseline in serum IL-18

    Time frame: each patient will be assessed one year after diagnosis

    Circulating levels of IL-18 are determined using high sensitivity Quantikine enzyme-linked immunosorbent assay (ELISA) and express as [pg/ml]

  6. Change from baseline in circulating levels of microRNA miR-30 and miR-7

    Time frame: each patient will be assessed one year after diagnosis

    Circulating levels of microRNA miR-30 and miR-7 are measured using TaqMan Advanced MicroRNA Assays

Sponsors and collaborators

Lead sponsor

University of Pisa

Other

Registry information

Official study title

P2X7 Receptor, Inflammation and Pathophysiology of Neurodegenerative Diseases

Acronym: NeuroInfiam

Important dates

Study start
2017
Primary completion
2018
Study completion
2019
First posted
Apr 17, 2019
Registry last updated
Aug 13, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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