Clinical trial NCT06965972: The CohorFES: a Prospective Study of Frailty and Dependence
Official title: Prospective Cohort for the Study of Phenotypic Clusters, Progression Paths and Outcomes of Frailty and Dependence: The Spanish CohorFES
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Frailty Syndrome
Keywords: COHORFES
Frailty
FTS5
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
Collaborators: name: Consorcio Centro de Investigación Biomédica en Red (CIBER)
name: CIBER on frailty and healthy ageing
First posted: 2025-05-11
Enrollment: 1500
Sex: ALL
Minimum age (years): 65
Maximum age (years): 120
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants are women and men 65 years old or above visited in the outpatient clinics of participant centers:

Hospital General Universitario Gregorio Marañón, Madrid Hospital Universitario de Getafe, Madrid Hospital General Universitario de Ciudad Real, Ciudad real Hospital del Mar, Consorci Mar Parc Salut de Barcelona, Barcelona Complejo Hospitalario Universitario de Albacete, Albacete Fundación del Hospital Nacional de Parapléjicos, Toledo

These participants are included in the COHORFES

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Fried phenotype
timeFrame: Through study completion, an average of 5 years
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
timeFrame: Through study completion, an average of 5 years
measure: Electronic Frailty index
timeFrame: Through study completion, an average of 5 years
Secondary outcomes:
measure: Bone Mineral Density
timeFrame: Through study completion, an average of 5 years
measure: Abnormal peripheral blood biochemistry
timeFrame: Through study completion, an average of 5 years
measure: Age
timeFrame: baseline
measure: Date of Birth
timeFrame: baseline
measure: Sex
timeFrame: baseline
measure: Living situation
timeFrame: baseline
measure: Educational level
timeFrame: baseline
measure: All-cause mortality.
timeFrame: From baseline until the date of death from any cause, an average of 5 years
measure: Condition diagnosis
timeFrame: Through study completion, an average of 5 years
measure: Usual treatments
timeFrame: Through study completion, an average of 5 years
measure: Pharmacy use
timeFrame: Through study completion, an average of 5 years
measure: Loss of weight
timeFrame: Through study completion, an average of 5 years
measure: Geriatric Depression Scale
timeFrame: Through study completion, an average of 5 years
measure: Barthel Index
timeFrame: Through study completion, an average of 5 years
measure: Lawton-Brody Instrumental Activities of Daily Living Scale
timeFrame: Through study completion, an average of 5 years
measure: Pfeiffer test
timeFrame: Through study completion, an average of 5 years
measure: Predimed questionnaire
timeFrame: Through study completion, an average of 5 years
measure: Healthcare resource use
timeFrame: Through study completion, an average of 5 years
measure: Non-elective hospital admissions
timeFrame: Through study completion, an average of 5 years
Other outcomes:
measure: Metabolomics
timeFrame: Through study completion, an average of 5 years
Locations:
city: Barcelona
country: Spain
facility: Hospital del Mar Research Institute
state: Catalonia
Study officials:
affiliation: Hospital del Mar
name: Xavier Nogues, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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