The CohorFES: a Prospective Study of Frailty and Dependence

Recruiting

• Conditions: Frailty Syndrome

• Registration Number: NCT06965972
• Lead Sponsor: Parc de Salut Mar

Brief Summary

Background Frailty has become a major problem for the health system, but also a window of opportunity to fight against disability through preventive strategies focused on the detection and treatment of frailty in all settings. However, no systematic strategies of screening and early detection are available in clinical settings. This project aims to identify clinical and biological phenotypic clusters that drive through the different stages of frailty and to describe the underlying mechanisms of the trajectories leading to disability and the potential for treatment. Moreover, validation of Frailty Trait Scale 5 (FTS5) will be performed as an easy model to be implemented in primary care and hospital scope.

Methods/design A prospective population-based cohort will be stablished for frailty phenotyping (CohorFES). Creation of a CIBERFES Biobank where blood and urine samples from participants of CohortFES are stored for future researches. Demographic and clinical history data, anthropometric measurements, predimed questionnaire, peripheral blood biochemical variables and metabolomics were collected for each participant at baseline and every year until become frailty.

Using cluster partition models (k-means and hierarchical clustering) will group together individuals with similar deficits and characteristics (frailty phenotypes). Then, by using pre-established criteria (gap and silhouette), the proposed clustering solution (belonging to given clusters) will be evaluated. Further, investigators will assess, in a longitudinal fashion, the appearance and accumulation of deficits during the study period and identifying the clusters subgroups with more rapid progression. Results will be applied to establish and compare clusters and trajectories. Finally, frailty phenotypes and patient clusters will be correlated with health outcomes such as the use of health services (both primary and secondary care), hospital admissions, and mortality.

Discussion Information about clinical and biological phenotypic clusters that drive through the different stages of frailty can lead to identify potential targets that could improve the therapeutic management of these patients.

In summary, from a research perspective the project aims to better understanding of the interindividual variability in clinical events that lead to frailty, dependence and finally, to death.

Detailed Description

1. Background of the study:

Frailty is one of the major challenges of the 21st Century, and a top priority for national and international organisms like the WHO (World Health Organization) or the European Parliament. This has put frailty as one of the top priorities in the biomedical research agenda of the European Commission. Frailty is constituted by a physiological state of increased vulnerability and impaired resilience to stressors (i.e. diseases, external agents, drugs tolerability and toxicity) due to the combined effect of the aging process and some chronic diseases which drives to a final stage of dependency and disability with a sharp impact in quality of life, health and social resources consumption, hospitalization and death.

It is well-known the relevance of frailty, its detection, and management since we are aware about their reversibility, the costs on the health systems, and its potential impact in clinical settings. In a clear contrast with the abundancy of data in non-clinical settings, there is a lack of strong data in the clinical setting where the prevalence of frailty is higher and where the risks for developing its most serious adverse consequences is more likely. There is hence an urgent need for a better screening and diagnosis of frailty, its trajectories and the determinants of these separate trajectories depending upon both the characteristics of frailty in each patient (associated or not with sarcopenia, or cognitive impairment or different clusters of chronic diseases).

2. Review of prior research:

While the different categories of the syndrome based on the severity of the observed deficits (robust, frail, pre-frail) are quite well defined and characterized from an epidemiological point of view, there is a scarcity of data on the functional pathways between these diagnostic categories (and, among them, disability), and this is especially true in clinical cohorts. This is really shocking considering that one of the most relevant factors, if not the first one, associated with a poor evolution of frailty is to experience an episode of hospitalization.

The overarching goal of this study is therefore, to identify the critical subgroups of subjects at risk of progression from robustness to prefrailty and frailty and from there to their late stages, and the pathways that mediate this trajectory amongst community-dwelling Spanish subjects.

Another important issue in this field would be to find an easy tool to identify frailty and factors which could be implemented in our full outpatients list. In addition to the more classical instruments to assess frailty, several groups currently members of CIBER on Frailty and Healthy Ageing (CIBERFES) developed an instrument that overcomes some of the problems raised by the more classical ones. The Frailty Trait Scale-FTS has shown a good predictive capacity for some outcomes in very old patients living in the community. More recently, and as part of an EU-funded project (FRAILTOOLS) we have found that the full version of FTS is able to detect frailty in some clinical settings (Acute Care Geriatric Unit, Geriatric Service outpatient office and Primary Care), with a good predictive capacity for adverse outcomes (death, incident disability, deterioration in SPPB, falls and hospitalization) at 6-12-18 months. However, the full version of FTS, composed of 12 items, takes around 15 minutes, making it unpractical in usual clinical conditions, where the time available by the physician or the nurse is lower. With this fact in mind, a shorter version of only 5 items (the so-called FTS 5) was developed.

This shorter version takes less time, but more interestingly, FTS 5 offers promising results based upon the sensitivity to detect small changes shown by the full FTS. Finally, the variables that compose the FTS5 (gait velocity, grip strength, BMI, PASE, and balance) can be incorporated into electronic instruments. This has been the case for the electronic frailty index (eFI), developed and validated in the British electronic records based on the Rockwood's frailty model that would allow to assess the frailty profile after to consider 36 items or deficits at the same moment of visit by primary care o hospital physician or the more recent Hospital Frailty Risk Score based on clinical diagnoses that is able to predict death but showing only a fair concordance with the Frailty Phenotype and the Frailty Index.

The use of easy electronic tools has been useful not only in hospital care but also in routine primary care practice. Moreover, it would be easier to measure the adverse outcomes, including falls, delirium, disability, care home admission, hospitalization and mortality as it has been recently shown.

3. Rationale of study:

Inside this conceptual framework and considering the scarce data available in clinical settings about frailty diagnosis, trajectories and prognosis, the main goal of this project is to stablish a clinical, real-life and prospective cohort (COHORFES) to identify clinical and biological phenotypic clusters that drive through the different stages of frailty and to identify the underlying mechanisms that finally will trigger the disability.

Study Timeline

• Study Start: 2022-12-01
• Status Verified: 2024-12
• Study First Submitted: 2025-04-07
• Study First Submitted QC: 2025-05-02
• Last Update Submitted: 2025-05-02
• Study First Posted: 2025-05-11
• Last Update Posted: 2025-05-11
• Primary Completion: 2030-12
• Study Completion: 2035-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1500

Inclusion Criteria

• women and men 65 years old or above visited in the outpatient clinics of participant centers
• Signed informed consent

Exclusion Criteria

• Patients in a critical situation of end of live or Barthel scale <60.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Fried phenotype	Through study completion, an average of 5 years	Frailty measure
Frailty Trait Scale 5 ítems: 1.- walking speed test, 2.- grip strength, 3.- Physical Activity, 4- Body Mass Index (BMI), 5.- progressive Romberg test. Point 1 to 5 are combined to report the frailty trait scale	Through study completion, an average of 5 years	Frailty measure
Electronic Frailty index	Through study completion, an average of 5 years	Frailty measure

Secondary Outcome Measures

Name	Time	Method
Age	baseline	Age in years
Date of Birth	baseline	Date (dd/mm/yyyy)
Sex	baseline	sex (Male or Female)
Living situation	baseline	Living situation: Alone or accompanied
Condition diagnosis	Through study completion, an average of 5 years	New condition diagnosis during follow-up (for ex. diagnosis of cancer, fracture, dementia, etc)
Usual treatments	Through study completion, an average of 5 years	treatments being taken by the patient
Pharmacy use	Through study completion, an average of 5 years	number of different drugs being taken by the patient
Educational level	baseline	Educational level: number of years in the school and college
All-cause mortality.	From baseline until the date of death from any cause, an average of 5 years	mortality during study follow-up (y/n)
Loss of weight	Through study completion, an average of 5 years	Loss of weight in the last year in grams
Geriatric Depression Scale	Through study completion, an average of 5 years	Geriatric Depression Scale: 15 items (y/n) were combined to report GDS
Barthel Index	Through study completion, an average of 5 years	Barthel Index: measure of functional disability
Bone Mineral Density	Through study completion, an average of 5 years	Bone Mineral Density measured using a Dual-Energy X-Ray Analysis (DXA) device (Hologic Horizon Wi, Hologic®).
Abnormal peripheral blood biochemistry	Through study completion, an average of 5 years	Detection of anormal values of the following parameters (y/n): * Leukocytes ml/mmc; * Red blood cells ml/mmc; * Hemoglobin g/dl; * Hematocrit %; * Red blood cell distribution width %; * Platelets ml/mmc; * Vitamin D ng/ml; * TSH nmol/l; * Glucose mg/dl; * Glycated hemoglobin (diabetics only) %; * Creatinine mg/dl; * Sodium meq/dl; * Potassium meq/dl; * Calcium mg/dl; * Phosphorus mg/dl; * GPT u/l; * GOT u/l; * Phosphatase alkaline u/l; * Total proteins g/dl; * Albumin g/dl; * Prealbumin mg/dl; * Cholesterol mg/dl; * Triglycerides mg/dl; * HDL mg/dl; * LDL mg/dl; * C-reactive protein mg/ml; These parameters are combined with the final outcome: abnormal biochemistry (y/n)
Lawton-Brody Instrumental Activities of Daily Living Scale	Through study completion, an average of 5 years	to assess independent living skills. It contains 8 items that are rated with a summary score from 0 (low functioning) to 8 (high functioning).
Pfeiffer test	Through study completion, an average of 5 years	test of 10 questions used to assess a person's cognitive status
Predimed questionnaire	Through study completion, an average of 5 years	The adherence of participants to the Mediterranean diet will be assessed through the 14-item Mediterranean diet adherence screener (MEDAS) validated for the Spanish population in a phone interview with the participant
Healthcare resource use	Through study completion, an average of 5 years	number of medical care consultations
Non-elective hospital admissions	Through study completion, an average of 5 years	Number of admissions in a Hospital

Trial Locations

Locations (1)

Hospital del Mar Research Institute; 🇪🇸 Barcelona, Catalonia, Spain