Effect of Infections and Global DNA Methylation on Frailty Trajectories in Hospitalized Older Patients (INFRAGEN) (INFRAGEN)

May 22, 2024 updated by: University Hospital of Ferrara

Effect of Infections and Global DNA Methylation on Frailty Trajectories in Hospitalized Older Patients: a Multicenter Observational Study (INFRAGEN)

This prospective multicenter study aims at exploring the impact of infections on intra-hospital and 3-month changes in the frailty profile of older inpatients.

To understand the complex pathways under the relationship between infections and frailty, this study will evaluate infection-related clinical and biochemical markers of systemic inflammation and genetics/epigenetics markers at ward admission.

The interplay between clinical, functional, and genetics/epigenetics factors will be evaluated in a subgroup of patients by testing whether 3-month changes in frailty concur with changes in the genomic DNA markers. This study will help characterize the pathophysiological mechanisms of frailty and identify at-risk conditions that may accelerate its course.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Infectious diseases are among the most common causes of hospitalization in older adults. Indeed, recent data report that more than 15% of hospital admissions in adults 65 years or older are due to infections, mainly in the urinary and respiratory tracts. Frailty is a well-known geriatric syndrome characterized by reduced individual resilience and increased vulnerability to external stressors. The prevalence of frailty ranges from around 10% in the community setting to almost 50% among institutionalized individuals.

Although both infectious diseases and frailty are associated with negative outcomes for the health of older adults and the healthcare system, their interplay has not been largely explored. In particular, it is not clear whether and to which extent acute infectious diseases might affect frailty, fastening its development or hampering its reversion.

The overall goal of the proposed project is to evaluate the impact of acute infections on frailty trajectories in older hospitalized patients from the pre-admission status to 3 months after hospital discharge. Moreover, a comprehensive set of sociodemographic, clinical, functional, and genetic/epigenetic factors will be assessed as possible effect modifiers in the association between infections and frailty trajectories.

This multicenter prospective observational study includes four geriatric wards (Ferrara, Padova, Milano, and Napoli) and involves individuals with no or mild-to-moderate frailty. A novel and interesting aspect will be represented by the analysis of genetic and epigenetic factors, i.e. global DNA methylation and telomere length. This point will make possible exploring the complex pathophysiologic mechanisms of frailty development using a translational approach involving both basic science and clinical researchers.

Overall, this study will help better identify at-risk conditions that may accelerate the course of frailty. Therefore, the project findings may promote the importance of interventions that could counteract frailty development during the hospital stay and should be addressed primarily to the categories of patients at highest risk.

Study Type

Observational

Enrollment (Estimated)

340

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

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

  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The project will involve older patients hospitalized in the Geriatric Units of the University Hospital of Ferrara, Padua, Monza, and Napoli. All patients non-frail or with mild frailty in the pre-admission period, and who will present a confirmed diagnosis of acute infection diseases at hospital admission or during the hospital stay, will be enrolled in the study.

Description

Inclusion Criteria:

  • confirmed diagnosis of acute infection diseases at hospital admission or during the hospital stay, according to specific ICD-9 codes with or without systemic inflammatory reaction;
  • pre-admission non-frailty or mild frailty assessed using the Clinical Frailty Scale (CFS < 6).

Exclusion Criteria:

  • terminally ill patients with an estimated life expectancy less than 3 months;
  • presence of pre-admission frailty (CFS ≥ 6);
  • unwillingness to participate in the study or to complete the follow-up assessments

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
Total sample
The study cohort will be composed of 340 older patients hospitalized in a Geriatric Unit with no or mild frailty in the pre-admission period, and who will present acute infections at admission or during the hospital stay.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in frailty index from pre-admission to hospital discharge
Time Frame: From 14 days before admission to hospital discharge (up to 60 days)
Frailty will be valuated through the Frailty Index (i.e. score from 0 to 1, with higher values corresponding to higher frailty), considering clinical and functional data. Pre-admission frailty will be retrospectively assessed to reflect the participant's status in the two weeks prior to the hospital admission. Frailty assessment will be repeated within 48h before the hospital discharge.
From 14 days before admission to hospital discharge (up to 60 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Clinical Frailty Scale from pre-admission to hospital discharge
Time Frame: From 14 days before admission to hospital discharge (up to 60 days)
Frailty will be evaluated through the Clinical Frailty Scale (i.e. score from 1 to 9, with higher values corresponding to higher frailty). Pre-admission frailty will be retrospectively assessed to reflect the participant's status in the two weeks prior to the hospital admission. Frailty assessment will be repeated within 48h before the hospital discharge.
From 14 days before admission to hospital discharge (up to 60 days)
Difference in in-hospital mortality between inpatients with vs without infections with systemic inflammation
Time Frame: From 14 days before admission to hospital discharge (up to 60 days)
All-cause mortality will be computed for participants with vs without infections associated with a systemic inflammatory response.
From 14 days before admission to hospital discharge (up to 60 days)
Difference in the length of hospital stay between inpatients with vs without infections with systemic inflammation
Time Frame: From 14 days before admission to hospital discharge (up to 60 days)
The length of hospital stay (number of days from hospital admission to hospital discharge) will be computed for participants with vs without infections associated with a systemic inflammatory response.
From 14 days before admission to hospital discharge (up to 60 days)
Difference in the global DNA methylation between individuals with stable vs worsened frailty during the hospital stay.
Time Frame: From 14 days before admission to hospital discharge (up to 60 days)
DNA extraction from whole blood will be performed by Automated Genomic DNA Purification EZ1 XL machine (QIAGEN). Global DNA methylation assessment will be performed by "highly quantitative pyrosequencing" technique as genome-wide DNA methylation levels and as gene promoter associated CpG islands utilizing selected age-related methylation marker loci and at LINE-1 repetitive elements (as a surrogate for genome-wide methylation). The patterns of global DNA methylation will be assessed in duplicate for each sample and expressed in percentage as the mean obtained by the two evaluations and considered valuable with a discrepancy <2%. Methylation percentages can be stratified into quartiles, and the middle two quartiles combined will be used as the reference category. The frequencies of individuals belonging to the highest and lowest DNA methylation quartiles will be compared between individuals reporting worsening in FI or CFS during the hospitalization vs those stable in frailty levels.
From 14 days before admission to hospital discharge (up to 60 days)
Difference in telomere length between individuals with stable vs worsened frailty during the hospital stay
Time Frame: From 14 days before admission to hospital discharge (up to 60 days)
Telomere length will be compared between individuals with stable vs worsened frailty during the hospital stay. DNA extraction from whole blood will be performed by Automated Genomic DNA Purification EZ1 XL machine (QIAGEN). Leukocyte Telomere Length (LTL) will be assessed by quantitative PCR as previously described as predictors of biological age in frailty and mortality association studies. As a measure of the relative Telomere length, the ratio of the telomere repeat copy number to the number of single-copy gene ratio (T/S ratio) will be determined by quantitative PCR using the single-copy gene 36B4 for reference and a standard curve. Quality controls and assay validation tests will be assessed by official commercial recognized standards (Qiagen, LifeTechnology).
From 14 days before admission to hospital discharge (up to 60 days)
Change in frailty index from hospital discharge to 3-month follow-up
Time Frame: From hospital discharge until 3 months after hospital discharge (time frame: 3 months)
Frailty will be valuated through the Frailty Index (i.e. score from 0 to 1, with higher values corresponding to higher frailty), considering clinical and functional data. Frailty assessment will be performed within 48h before the hospital discharge and after 3-month from the hospital discharge.
From hospital discharge until 3 months after hospital discharge (time frame: 3 months)
Change in Clinical Frailty Scale from hospital discharge to 3-month follow-up
Time Frame: From hospital discharge until 3 months after hospital discharge (time frame: 3 months)
Frailty will be evaluated through the Clinical Frailty Scale (i.e. score from 1 to 9, with higher values corresponding to higher frailty). Frailty assessment will be performed within 48h before the hospital discharge and after 3-month from the hospital discharge.
From hospital discharge until 3 months after hospital discharge (time frame: 3 months)

Collaborators and Investigators

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

Sponsor

University Hospital of Ferrara

Collaborators

Azienda Ospedaliera Universitaria Policlinico
Azienda Ospedaliera di Padova
Fondazione IRCCS San Gerardo dei Tintori

Investigators

  • Principal Investigator: Stefano Volpato, MD, Università degli Studi di Ferrara

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Estimated)

May 20, 2024

Primary Completion (Estimated)

September 1, 2025

Study Completion (Estimated)

March 1, 2026

Study Registration Dates

First Submitted

March 26, 2024

First Submitted That Met QC Criteria

May 22, 2024

First Posted (Actual)

May 28, 2024

Study Record Updates

Last Update Posted (Actual)

May 28, 2024

Last Update Submitted That Met QC Criteria

May 22, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 83/2023/Oss/AOUFe

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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