Biological Aging, Medication, Malnutrition and Inflammation Among Acutely Ill and Healthy Elderly. (FAM-CPH)

In this study, the investigators will investigate and characterize acute medical patients in order to optimize patient courses in the acute care departments, especially with regard to polypharmacy and undernourishment. In addition, the investigators will investigate underlying immunological mechanisms of chronic inflammation and biological aging in this population to improve the current knowledge and possibilities for preventing chronic diseases and acute hospitalization.

Study Overview

• Status: Unknown
• Conditions: Inflammation; Malnutrition; Aging; Polypharmacy; Emergency Service, Hospital

Detailed Description

Malnutrition:

Malnutrition among elderly is associated with frailty, including loss of weight, muscle mass, function and quality of life and also with an increased number of hospital admissions. In this study, the investigators aim to describe the development of and the risk factors for malnutrition from admission to 4 weeks after discharge, in addition the investigators wish to characterize the inflammatory state of the malnourished patients.

Inappropriate polypharmacy:

The broad variation among elderly in health, number of chronic diseases, organ function, biological age and function makes the prescription of drugs to this population a very complex task with a high risk of inappropriate medication. 5-30% of all non-elective admissions are caused by inappropriate medications, and many of these are preventable. Therefore, the investigators aim to investigate the feasibility of a pharmacist-geriatrician medication review in the acute care department and the effect on the Medication Appropriateness Index score (MAI-score) .

Chronic inflammation and biological aging:

Chronic inflammation and biological aging promote the development of age-related chronic diseases. There is a large variation in the rate of aging between individuals, in particular among the elderly. This means that the chronological age of a person often does not reflect its true state of aging, the biological age. This challenges the ability to provide appropriate care and to predict responses to treatment and interventions in elderly patients. The underlying causes and mechanisms of biological aging and chronic inflammation are not well understood. There are currently no validated methods for measuring biological age and no measures of chronic inflammation which can be used in an acute setting. Here, the investigators aim to test a novel model for chronic inflammation and investigate the role of the NLRP3 inflammasome, NFkB (nuclear factor kappa light chain enhancer of activated B cells) and miRNAs in biological aging and chronic inflammation.

The study is prospective with 3 groups of study participants: one group is included in the Acute Medical Department and two healthy control groups (one young and one older). The follow-up comprises two predefined examinations and any readmissions at our hospital. Furthermore, participants are followed in the national registries.

• Study Type: Observational
• Enrollment (Anticipated): 212

Contacts and Locations

Study Locations

• Denmark
  • Region Hovedstaden
    • Hvidovre, Region Hovedstaden, Denmark, 2650
      • Amager & Hvidovre Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 110 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Three study groups; the FAM group, control group 1 and control group 2

Description

FAM group:

Inclusion Criteria:

• ≥65 years
• Acute medical patient
• Understands and speaks Danish

Exclusion Criteria:

• Unable to cooperate cognitively
• Terminal patients
• Patients in isolation

Control group 1:

Inclusion Criteria:

• ≥65 years
• No hospital admissions within the past 2 years

Exclusion Criteria:

• Acute admissions within the past 2 years
• Auto-immune diseases
• Treatment with immunosuppressive or biological therapies

Control group 2:

Inclusion Criteria:

• 20-35 years
• Caucasian
• No admissions due to chronic or critical illness within the past 5 years (except admissions related to child birth, abortion, appendicitis, poisoning, traumas, concussion etc.)

Exclusion Criteria:

• Auto-immune or chronic diseases

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
FAM group (n=98); ≥65 years. Acutely admitted medical patients. Included consecutively at admission to the Acute Medical Department at Amager and Hvidovre Hospital and Rigshospitalet - Glostrup. Follow-up at 4 weeks and 56 weeks after discharge and at any readmissions in the study period. Participants are interviewed on physical, mental and nutritional status, tested for functional and cognitive status, and have anthropometry, biochemistry, blood pressure, and immune activity measured. Participants are followed in national registries for information on diagnoses, hospital admissions, health care services used, and mortality. If a patient uses ≥5 prescribed drugs before hospitalization, a medication review will be performed by a clinical pharmacist and a geriatrician. Sample size calculations were performed for each primary outcome, and the final sample size was based on the calculation for the eating validation scheme which resulted in the largest sample size.
Control group 1 (n=54); ≥65 years. No hospital admissions within the past two years. Matched individually with patients in the FAM group by age, sex, and municipality. Examined at inclusion and 52 weeks after inclusion. Participants are interviewed on physical, mental and nutritional status, tested for functional and cognitive status, and have anthropometry, biochemistry, blood pressure, and immune activity measured. Participants are followed in national registries for information on diagnoses, hospital admissions, health care services used, and mortality.
Control group 2 (n=60); 20-35 years No admissions due to chronic or critical illness within the past 5 years (except admissions related to child birth, abortion, appendicitis, poisoning, traumas, concussion etc.) Examined at inclusion and 4 weeks after inclusion. The examination includes a questionnaire about life style, a physical examination, and blood samples.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eating validation scheme score	Development in nutritional status and risk factors of malnutrition within the FAM group.	From inclusion to 4 weeks after discharge
MAI score (Medication Appropriateness Index)	Difference in summed MAI-score per patient. MAI score between inclusion and first follow-up visit (FAM group)	From inclusion to 4 weeks after discharge
NF-kB (Nuclear Factor Kappa light chain enhancer og activated B cells) activity	The development in NF-kB activity between the groups will be investigated. The association of NF-kB activity with biological ageing-measured by chronic inflammation, and loss of function and cognition-will also be investigated.	From inclusion to 56 weeks after discharge
Chronic inflammation	Stability and discriminative ability of new model for chronic inflammation (Control group 2)	From inclusion to 4 weeks after inclusion
NLRP3 activity	Difference in NLRP3 inflammasome activity between groups.	From inclusion to 56 weeks after discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bodyweight (kg)	Development in bodyweight	From inclusion to 4 and 56 weeks after discharge
Quality of life	EQ-5D-5L(EuroQol-5Dimentions-5Llevels), mini geriatric depression score	From inclusion to 56 weeks after discharge
Medication under-prescribing	Assessment of underutilization Index (AOU)	From inclusion to 4 weeks after discharge
Inflammation in malnourished patients	Characterize the level of inflammation in malnourished patients	4 weeks after discharge
Functional recovery score	Assessing activities of daily living to characterize development in physical performance	From inclusion to 56 weeks after discharge
Cystatin C		From inclusion to 56 weeks after discharge
Cytokine concentrations	The concentration of cytokines at baseline and in response to stimulation will be measured	From inclusion to 56 weeks after discharge
Cytometry	Characterization of immune cell subsets	From inclusion to 56 weeks after discharge
miRNA	Levels of miRNA will be measured, and their association with NF-kB activity and biological ageing will be investigated.	From inclusion to 56 weeks after discharge
NF-kB activation	The activation of NF-kB in response to stimulation.	From inclusion to 56 weeks after discharge
C-reactive protein (inflammation)	Difference in inflammation between groups	From inclusion to 56 weeks after discharge
Soluble urokinase plasminogen activator receptor (suPAR) (ng/ml)	The plasma level of suPAR is a measure of inflammation and can be used to assess the difference in inflammation between groups	From inclusion to 56 weeks after discharge
Frequency of physicians' acceptance of suggested changes in medications		At inclusion and at 4 weeks after discharge in the FAM group

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sit-to-stand test	Development in physical performance	From inclusion to 56 weeks after discharge
Cognitive functional ability	Orientation memory concentration, mini mental state examination, Hopkins verbal learning test, trail making test, digit symbol substitution test	From inclusion to 56 weeks after discharge
Waist circumference (cm)		From inclusion to 56 weeks after discharge
Handgrip strength (kg) of dominant hand	Development in physical performance	From inclusion to 56 weeks after discharge
Habitual 4 m gait speed (m/s)	Development in physical performance	From inclusion to 56 weeks after discharge
Plasma and serum concentrations of admission blood samples	Routinely analyzed physiological biomarkers measured in plasma and serum	From inclusion to 56 weeks after discharge
Blood concentration of cholesterol and triglycerides		From inclusion to 56 weeks after discharge
Blood concentration of metabolic markers	Measurement of insulin, blood glucose, and HbA1c	From inclusion to 56 weeks after discharge
Plasma concentration of active drug substances		From inclusion to 56 weeks after discharge
CMV-IgG (Cytomegalovirus-immunoglobulin G)	Cytomegalovirus IgG titer	From inclusion to 56 weeks after discharge

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Collaborators: Lundbeck Foundation; Region Hovedstadens Apotek; Clinical Research Centre
• Investigators: Principal Investigator: Morten B. Houlind, MSc, Hvidovre University Hospital; Principal Investigator: Juliette Tavenier, MSc, Hvidovre University Hospital; Principal Investigator: Line JH Rasmussen, MSc, Hvidovre University Hospital; Principal Investigator: Aino L Andersen, MSc, Hvidovre University Hospital

Publications and helpful links

General Publications

• Bornaes O, Andersen AL, Houlind MB, Kallemose T, Tavenier J, Aharaz A, Nielsen RL, Jorgensen LM, Beck AM, Andersen O, Petersen J, Pedersen MM. Mild Cognitive Impairment Is Associated with Poorer Nutritional Status on Hospital Admission and after Discharge in Acutely Hospitalized Older Patients. Geriatrics (Basel). 2022 Sep 10;7(5):95. doi: 10.3390/geriatrics7050095.

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: January 5, 2017
• First Submitted That Met QC Criteria: February 9, 2017
• First Posted (Actual): February 14, 2017

Study Record Updates

• Last Update Posted (Actual): October 15, 2019
• Last Update Submitted That Met QC Criteria: October 14, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Nutrition Disorders; Emergencies; Inflammation; Malnutrition
• Other Study ID Numbers: FAM-CPH-cohort; H-16038786 (Other Identifier: Committees on Health Research Ethics); AHH-2016-067 (I-suite 04931) (Other Identifier: Danish Data Protection Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO