Clinical trial NCT06430073: Effect of Infections and Global DNA Methylation on Frailty Trajectories in Hospitalized Older Patients (INFRAGEN)
Official title: Effect of Infections and Global DNA Methylation on Frailty Trajectories in Hospitalized Older Patients: a Multicenter Observational Study (INFRAGEN)
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Aging
Frailty
Telomere Shortening
Inflammation
Hospital Infection
Lead sponsor: University Hospital of Ferrara
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliera di Padova
name: Fondazione IRCCS San Gerardo dei Tintori
name: Azienda Ospedaliera Universitaria Policlinico
First posted: 2024-05-28
Enrollment: 340
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in frailty index from pre-admission to hospital discharge
timeFrame: From 14 days before admission to hospital discharge (up to 60 days)
Secondary outcomes:
measure: Change in Clinical Frailty Scale from pre-admission to hospital discharge
timeFrame: From 14 days before admission to hospital discharge (up to 60 days)
measure: Difference in in-hospital mortality between inpatients with vs without infections with systemic inflammation
timeFrame: From 14 days before admission to hospital discharge (up to 60 days)
measure: Difference in the length of hospital stay between inpatients with vs without infections with systemic inflammation
timeFrame: From 14 days before admission to hospital discharge (up to 60 days)
measure: Difference in the global DNA methylation between individuals with stable vs worsened frailty during the hospital stay.
timeFrame: From 14 days before admission to hospital discharge (up to 60 days)
measure: Difference in telomere length between individuals with stable vs worsened frailty during the hospital stay
timeFrame: From 14 days before admission to hospital discharge (up to 60 days)
measure: Change in frailty index from hospital discharge to 3-month follow-up
timeFrame: From hospital discharge until 3 months after hospital discharge (time frame: 3 months)
measure: Change in Clinical Frailty Scale from hospital discharge to 3-month follow-up
timeFrame: From hospital discharge until 3 months after hospital discharge (time frame: 3 months)
Other outcomes:
Locations:
Study officials:
affiliation: Università degli Studi di Ferrara
name: Stefano Volpato, MD
role: PRINCIPAL_INVESTIGATOR
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