P2X7 Receptor, Inflammation and Neurodegenerative Diseases

NCT ID: NCT03918616

Last Updated: 2019-08-13

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-02-20
• Study Completion Date: 2019-03-30

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.

Detailed Description

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.

Conditions

Neuro-Degenerative Disease

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Memantine, Dopamine receptor-agonists

Intervention Type: DRUG

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

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.

No interventions assigned to this group

Interventions

Memantine, Dopamine receptor-agonists

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

Intervention Type: DRUG

Other Intervention Names

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

Eligibility Criteria

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.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pisa

OTHER

Sponsor Role: lead

Responsible Party

Anna Solini

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anna Solini, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Univeristy of Pisa

Locations

University of Pisa

Pisa, , Italy

Countries

Italy

Other Identifiers

AS0002

Identifier Type: -

Identifier Source: org_study_id