PIPAF Platelets in the Pathogenesis of Ageing Associated Frailty

Coronary Artery Disease Clinical Trial

— PIPAF  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05798637
• Other study ID #: 3546/19
• Status: Recruiting
• Start date: February 10, 2020
• Est. completion date: November 2023

Study information

• Verified date: April 2023
• Source: Azienda Ospedaliera di Perugia
• Contact: Paolo Gresele, Prof
• Phone: 07.55783989
• Email: paolo.gresele[@]unipg.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: November 2023
• Est. primary completion date: November 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Coronary Artery Disease
• Coronary Disease
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Frailty
• Myocardial Ischemia

Intervention

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)

Locations

Country	Name	City	State
Italy	IRCCS Centro Cardiologico Monzino	Milano	Milan
Italy	Univeristà di Pavia	Pavia

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera di Perugia

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of platelet activation	Platelet activation will be assessed in vivo, on circulating platelets, by flowcytometry measurement of p-selectin, integrin aIIbß3, and tissue factor expression, and in vitro, on isolated platelets, by studying the response to agonists (thrombin, ADP, collagen) with lumiaggregometry and ATP secretion	3 years
Secondary	Rate of systemic inflammation and oxidative stress	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.	3 years
Secondary	Procoagulant platelet activity	Platelet procoagulant activity will be measured by quantifying thrombin generation from lysed platelets using the Calibrated Automated Thrombogram Assay	3 years
Secondary	Rate of proinflammatory platelet activity	Proinflammatory platelet capacity will be estimated by measuring the expression of matrix metalloproteinases MMP-2 and MMP-9.	3 years
Secondary	Rate of platelet heterogeneity	Platelets with procoagulant and proinflammatory activity will be identified by flowcytometry, and their transcripts/micro RNAs will be analyzed in the different patient groups	3 years