PIPAF Platelets in the Pathogenesis of Ageing Associated Frailty

Recruiting

• Conditions: Coronary Artery Disease; Diabetes Mellitus, Type 2; Alzheimer Disease
• Interventions: Other: Standard of care

• Registration Number: NCT05798637
• Lead Sponsor: Azienda Ospedaliera di Perugia

Brief Summary

This is a prospective observational study aimed at testing the existence of an association between frailty, inflammatory status, and degree of platelet activation and reactivity in elderly subjects with type 2 diabetes or coronary artery disease or Alzheimer's disease.

Detailed Description

Frailty in the elderly is a syndrome that strongly affects quality of life and represents a major social and economic challenge. Frailty often, and more frequently, occurs in individuals with aging-related diseases including type 2 diabetes, cardiovascular disease, and Alzheimer's disease. All of these diseases are associated with a state of weak chronic inflammation. Studies in recent years have pointed out that platelets can directly contribute to inflammatory processes. Due to of this ability to act as proinflammatory cells and of their strong involvement in various metabolic, cardiovascular, and neurodegenerative disorders, platelets appear to have key roles in the physio-pathological mechanisms that predispose to frailty.

In the present study, it is planned to recruit 4 cohorts of elderly patients, each of 40 patients, divided by pathology ( frail elderly, diabetic elderly, elderly with stable atherosclerotic coronary artery disease, elderly with early-stage Alzheimer's disease) and a cohort of 40 healthy elderly subjects. All subjects will perform a blood draw at enrollment and after 24 months of follow up in order to evaluate: the state of platelet activation; the aggregating response of platelets to stimuli such as thrombin, Adenosine DiPhosphate (ADP), and collagen; the state of chronic inflammation and oxidative stress; the procoagulant profile of platelets; presence of platelet subpopulations characterized by RNA, microRNA and/or protein profiling. Each subject will also be given a questionnaire to assess frailty status (according to Fried's criteria) and urine samples will be collected to perform the assay of metabolites such as 11dh-TXB, 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-epiPGF2a (8-isoprostane).

Study Timeline

• Study Start: 2020-02-10
• Study First Submitted: 2023-03-23
• Study First Submitted QC: 2023-03-23
• Status Verified: 2023-04
• Study First Posted: 2023-04-04
• Last Update Submitted: 2023-04-04
• Last Update Posted: 2023-04-06
• Primary Completion: 2023-11
• Study Completion: 2023-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• age > 65 years
• low-dose aspirin therapy (100 mg)
• belonging to each of the cohorts indicated

Exclusion Criteria

• Lack of inclusion criteria and/or consent to the study

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Group A	Standard of care	Elderly subjects diagnosed with coronary syndrome ascertained by coronary angiography
Group D	Standard of care	Elderly subjects with alzheimer's disease
Group B	Standard of care	Frail elderly
Group C	Standard of care	Elderly subjects with type 2 diabetes mellitus
Group E	Standard of care	Not frail elderly subjects

Primary Outcome Measures

Name	Time	Method
Rate of platelet activation	3 years	Platelet activation will be assessed in vivo, on circulating platelets, by flowcytometry measurement of p-selectin, integrin αIIbβ3, and tissue factor expression, and in vitro, on isolated platelets, by studying the response to agonists (thrombin, ADP, collagen) with lumiaggregometry and ATP secretion

Secondary Outcome Measures

Name	Time	Method
Rate of systemic inflammation and oxidative stress	3 years	Quantification of oxidative stress and chronic inflammation will be done by measuring the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-epiPGF2a (8-isoprostane) on urine and the levels of high-sensitivity PCR, sCD40L, sRAGE, TAT and F1+2 in plasma by enzyme immunoassay method.
Procoagulant platelet activity	3 years	Platelet procoagulant activity will be measured by quantifying thrombin generation from lysed platelets using the Calibrated Automated Thrombogram Assay
Rate of platelet heterogeneity	3 years	Platelets with procoagulant and proinflammatory activity will be identified by flowcytometry, and their transcripts/micro RNAs will be analyzed in the different patient groups
Rate of proinflammatory platelet activity	3 years	Proinflammatory platelet capacity will be estimated by measuring the expression of matrix metalloproteinases MMP-2 and MMP-9.

Trial Locations

Locations (2)

Univeristà di Pavia; 🇮🇹 Pavia, Italy

IRCCS Centro Cardiologico Monzino; 🇮🇹 Milano, Milan, Italy