PIPAF Platelets in the Pathogenesis of Ageing Associated Frailty

Sponsor

Azienda Ospedaliera di Perugia (Other)

Overall Status

Recruiting

CT.gov ID

NCT05798637

Collaborator

(none)

200

Enrollment

Locations

44.7

Anticipated Duration (Months)

100

Patients Per Site

2.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease Diabetes Mellitus, Type 2 Alzheimer Disease	Other: Standard of care

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 Design

Study Type:

Observational

Anticipated Enrollment :

200 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Role of Inflammation in the Pathogenesis of Frailty in the Elderly: Studies on the Contribution of Blood Platelets- PIPAF Platelets in the Pathogenesis of Ageing Associated Frailty

Actual Study Start Date :

Feb 10, 2020

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Group A Elderly subjects diagnosed with coronary syndrome ascertained by coronary angiography	Other: Standard of care No treatment other than clinical standard therapy is provided. Each subjects will perform a blood draw at enrollment and after 24 months of follow-up. Subjects will also be given a frailty status assessment questionnaire (according to the criteria of Fried)
Group B Frail elderly	Other: Standard of care No treatment other than clinical standard therapy is provided. Each subjects will perform a blood draw at enrollment and after 24 months of follow-up. Subjects will also be given a frailty status assessment questionnaire (according to the criteria of Fried)
Group C Elderly subjects with type 2 diabetes mellitus	Other: Standard of care No treatment other than clinical standard therapy is provided. Each subjects will perform a blood draw at enrollment and after 24 months of follow-up. Subjects will also be given a frailty status assessment questionnaire (according to the criteria of Fried)
Group D Elderly subjects with alzheimer's disease	Other: Standard of care No treatment other than clinical standard therapy is provided. Each subjects will perform a blood draw at enrollment and after 24 months of follow-up. Subjects will also be given a frailty status assessment questionnaire (according to the criteria of Fried)
Group E Not frail elderly subjects	Other: Standard of care No treatment other than clinical standard therapy is provided. Each subjects will perform a blood draw at enrollment and after 24 months of follow-up. Subjects will also be given a frailty status assessment questionnaire (according to the criteria of Fried)

Outcome Measures

Primary Outcome Measures

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

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 proinflammatory platelet activity [3 years]
Proinflammatory platelet capacity will be estimated by measuring the expression of matrix metalloproteinases MMP-2 and MMP-9.
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