P2X7 Receptor, Inflammation and Neurodegenerative Diseases

NCT03918616 | Completed

• 1 other identifier: AS0002
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neuro-Degenerative Disease

Keywords

Alzheimer disease; Parkinson disease; P2X7 receptor

Outcome Measures

Primary Outcomes (6)

• Change from baseline in P2X7R-inflammasome activity

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

  each patient will be assessed one year after diagnosis

• Change from baseline in NFkB activity

  NFkB activity is measured using RT-PCR

  each patient will be assessed one year after diagnosis

• Change from baseline in serum α-synuclein

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

  each patient will be assessed one year after diagnosis

• Change from baseline in serum IL-1β

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

  each patient will be assessed one year after diagnosis

• Change from baseline in serum IL-18

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

  each patient will be assessed one year after diagnosis

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

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

  each patient will be assessed one year after diagnosis

Study Arms (2)

PD + AD

Patients with newly-diagnosed (onset of suggestive symptoms not later than 3 months) Parkinson disease (PD) or Alzheimer disease (AD) with no previous specific treatment, no anti-inflammatory drugs assumed in the three months preceding the enrolment and no chronic inflammatory diseases or cancer.

Drug: Memantine, Dopamine receptor-agonists

Control group

An age and gender matched control group (n=50) was formed, on a volunteer basis, by the spouse of the probands participating in the study.

Interventions

Memantine, Dopamine receptor-agonists DRUG

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

Also known as: Memantine: Ebixa. Dopamine receptor-agonists: Sinemet, Sirio.

PD + AD

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study consecutively enrolled 50 newly-diagnosed, treatment-naive PD or AD individuals among those referring to the Neurology Unit, University Hospital in Pisa, Italy.

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• University of Pisa: lead

Study Sites (1)

University of Pisa

Pisa, 56125, Italy

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum samples

MeSH Terms

Conditions

Alzheimer Disease; Parkinson Disease

Interventions

Memantine; Dopamine Agonists; sirio

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs

Study Officials

• Anna Solini, MD, PhD

  Univeristy of Pisa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 10, 2019
• First Posted: April 17, 2019
• Study Start: February 20, 2017
• Primary Completion: December 30, 2018
• Study Completion: March 30, 2019
• Last Updated: August 13, 2019

Record last verified: 2019-08

Locations

IT (1)