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

NCT06430073 | Not Yet Recruiting

• 1 other identifier: 83/2023/Oss/AOUFe
• Study Type: observational
• Target: 340
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Aging; Frailty; Telomere Shortening; Inflammation; Hospital Infection

Outcome Measures

Primary Outcomes (1)

• Change in frailty index from pre-admission to hospital discharge

  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 Outcomes (7)

• Change in Clinical Frailty Scale from pre-admission to 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

  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

  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.

  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

  From 14 days before admission to hospital discharge (up to 60 days)

Study Arms (1)

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.

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)
• 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.

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital of Ferrara: lead
• Azienda Ospedaliera di Padova: collaborator
• Fondazione IRCCS San Gerardo dei Tintori: collaborator
• Azienda Ospedaliera Universitaria Policlinico: collaborator

Related Publications (17)

• Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014 Jun;69 Suppl 1:S4-9. doi: 10.1093/gerona/glu057.

  PMID: 24833586 BACKGROUND

• Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. doi: 10.1093/gerona/56.3.m146.

  PMID: 11253156 BACKGROUND

• Greco GI, Noale M, Trevisan C, Zatti G, Dalla Pozza M, Lazzarin M, Haxhiaj L, Ramon R, Imoscopi A, Bellon S, Maggi S, Sergi G. Increase in Frailty in Nursing Home Survivors of Coronavirus Disease 2019: Comparison With Noninfected Residents. J Am Med Dir Assoc. 2021 May;22(5):943-947.e3. doi: 10.1016/j.jamda.2021.02.019. Epub 2021 Feb 22.

  PMID: 33757725 BACKGROUND

• Huoman J, Sayyab S, Apostolou E, Karlsson L, Porcile L, Rizwan M, Sharma S, Das J, Rosen A, Lerm M. Epigenetic rewiring of pathways related to odour perception in immune cells exposed to SARS-CoV-2 in vivo and in vitro. Epigenetics. 2022 Dec;17(13):1875-1891. doi: 10.1080/15592294.2022.2089471. Epub 2022 Jun 26.

  PMID: 35758003 BACKGROUND

• Iwai-Saito K, Shobugawa Y, Aida J, Kondo K. Frailty is associated with susceptibility and severity of pneumonia in older adults (A JAGES multilevel cross-sectional study). Sci Rep. 2021 Apr 12;11(1):7966. doi: 10.1038/s41598-021-86854-3.

  PMID: 33846416 BACKGROUND

• Lapham K, Kvale MN, Lin J, Connell S, Croen LA, Dispensa BP, Fang L, Hesselson S, Hoffmann TJ, Iribarren C, Jorgenson E, Kushi LH, Ludwig D, Matsuguchi T, McGuire WB, Miles S, Quesenberry CP Jr, Rowell S, Sadler M, Sakoda LC, Smethurst D, Somkin CP, Van Den Eeden SK, Walter L, Whitmer RA, Kwok PY, Risch N, Schaefer C, Blackburn EH. Automated Assay of Telomere Length Measurement and Informatics for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort. Genetics. 2015 Aug;200(4):1061-72. doi: 10.1534/genetics.115.178624. Epub 2015 Jun 19.

  PMID: 26092717 BACKGROUND

• Park CM, Kim W, Rhim HC, Lee ES, Kim JH, Cho KH, Kim DH. Frailty and hospitalization-associated disability after pneumonia: A prospective cohort study. BMC Geriatr. 2021 Feb 5;21(1):111. doi: 10.1186/s12877-021-02049-5.

  PMID: 33546614 BACKGROUND

• Prampart S, Le Gentil S, Bureau ML, Macchi C, Leroux C, Chapelet G, de Decker L, Rouaud A, Boureau AS. Functional decline, long term symptoms and course of frailty at 3-months follow-up in COVID-19 older survivors, a prospective observational cohort study. BMC Geriatr. 2022 Jun 30;22(1):542. doi: 10.1186/s12877-022-03197-y.

  PMID: 35768781 BACKGROUND

• Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci. 2007 Jul;62(7):722-7. doi: 10.1093/gerona/62.7.722.

  PMID: 17634318 BACKGROUND

• Schneider CV, Schneider KM, Teumer A, Rudolph KL, Hartmann D, Rader DJ, Strnad P. Association of Telomere Length With Risk of Disease and Mortality. JAMA Intern Med. 2022 Mar 1;182(3):291-300. doi: 10.1001/jamainternmed.2021.7804.

  PMID: 35040871 BACKGROUND

• Schork NJ, Beaulieu-Jones B, Liang W, Smalley S, Goetz LH. Does Modulation of an Epigenetic Clock Define a Geroprotector? Adv Geriatr Med Res. 2022;4(1):e220002. doi: 10.20900/agmr20220002. Epub 2022 Mar 29.

  PMID: 35466328 BACKGROUND

• Seligman BJ, Berry SD, Lipsitz LA, Travison TG, Kiel DP. Epigenetic Age Acceleration and Change in Frailty in MOBILIZE Boston. J Gerontol A Biol Sci Med Sci. 2022 Sep 1;77(9):1760-1765. doi: 10.1093/gerona/glac019.

  PMID: 35037036 BACKGROUND

• Vetter VM, Kalies CH, Sommerer Y, Spira D, Drewelies J, Regitz-Zagrosek V, Bertram L, Gerstorf D, Demuth I. Relationship Between 5 Epigenetic Clocks, Telomere Length, and Functional Capacity Assessed in Older Adults: Cross-Sectional and Longitudinal Analyses. J Gerontol A Biol Sci Med Sci. 2022 Sep 1;77(9):1724-1733. doi: 10.1093/gerona/glab381.

  PMID: 35032170 BACKGROUND

• Vlachogiannis NI, Baker KF, Georgiopoulos G, Lazaridis C, Schim van der Loeff I, Hanrath AT, Sopova K, Tual-Chalot S, Gatsiou A, Spyridopoulos I, Stamatelopoulos K, Duncan CJA, Stellos K. Clinical frailty, and not features of acute infection, is associated with late mortality in COVID-19: a retrospective cohort study. J Cachexia Sarcopenia Muscle. 2022 Jun;13(3):1502-1513. doi: 10.1002/jcsm.12966. Epub 2022 Mar 7.

  PMID: 35257497 BACKGROUND

• Wang J, Maxwell CA, Yu F. Biological Processes and Biomarkers Related to Frailty in Older Adults: A State-of-the-Science Literature Review. Biol Res Nurs. 2019 Jan;21(1):80-106. doi: 10.1177/1099800418798047. Epub 2018 Sep 9.

  PMID: 30198309 BACKGROUND

• Yoshikawa TT, Norman DC. Geriatric Infectious Diseases: Current Concepts on Diagnosis and Management. J Am Geriatr Soc. 2017 Mar;65(3):631-641. doi: 10.1111/jgs.14731. Epub 2017 Jan 31.

  PMID: 28140454 BACKGROUND

• Guo W, Bencivenga L, Zanforlini BM, Curreri C, Ferrara MC, Maisano B, Tinelli L, Ceparano LA, Merenda R, Cosma C, Manfron L, Gentili N, Sturani S, Cardi M, Campion A, Berardi B, Lombardi M, D'Aversa E, Salvatori F, Tisato V, Vargas JV, Femminella GD, Gemmati D, Sergi G, Bellelli G, Mazzola P, Trevisan C, Volpato S; INFRAGEN working group. Effect of infections, DNA methylation and telomere length on frailty trajectories in hospitalized older patients: the INFRAGEN study protocol. BMC Geriatr. 2025 Jul 23;25(1):545. doi: 10.1186/s12877-025-06194-z.

  PMID: 40702442 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood sample

MeSH Terms

Conditions

Frailty; Inflammation; Cross Infection

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Iatrogenic Disease; Disease Attributes

Study Officials

• Stefano Volpato, MD

  Università degli Studi di Ferrara

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caterina Trevisan, PhD

CONTACT

+393896743650; caterina.trevisan@unife.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2024
• First Posted: May 28, 2024
• Study Start: May 20, 2024
• Primary Completion: September 1, 2025
• Study Completion: March 1, 2026
• Last Updated: May 28, 2024

Record last verified: 2024-03