PIPAF Platelets in the Pathogenesis of Ageing Associated Frailty (PIPAF)

April 4, 2023 updated by: Paolo Gresele, Azienda Ospedaliera di Perugia

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Anticipated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

The study involves 5 cohorts of patients:

  • patients diagnosed with stable ischemic heart disease (CAD)
  • frail elderly patients
  • patients with type 2 diabetes (T2DM)
  • patients with Alzheimer's disease (AD)
  • not frail elderly subjects (control group).

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of platelet activation
Time Frame: 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
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Procoagulant platelet activity
Time Frame: 3 years
Platelet procoagulant activity will be measured by quantifying thrombin generation from lysed platelets using the Calibrated Automated Thrombogram Assay
3 years
Rate of systemic inflammation and oxidative stress
Time Frame: 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.
3 years
Rate of proinflammatory platelet activity
Time Frame: 3 years
Proinflammatory platelet capacity will be estimated by measuring the expression of matrix metalloproteinases MMP-2 and MMP-9.
3 years
Rate of platelet heterogeneity
Time Frame: 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
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Ospedaliera di Perugia

Investigators

  • Principal Investigator: Paolo Gresele, Prof, Universita degli Studi di Perugia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 10, 2020

Primary Completion (Anticipated)

November 1, 2023

Study Completion (Anticipated)

November 1, 2023

Study Registration Dates

First Submitted

March 23, 2023

First Submitted That Met QC Criteria

March 23, 2023

First Posted (Actual)

April 4, 2023

Study Record Updates

Last Update Posted (Actual)

April 6, 2023

Last Update Submitted That Met QC Criteria

April 4, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3546/19

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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