Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT04413877 |
| Other study ID # |
GerULiege/SG/DSR/ICOPE |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
December 1, 2023 |
| Est. completion date |
December 1, 2023 |
Study information
| Verified date |
December 2023 |
| Source |
University of Liege |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Introduction: The World Health Organization has launched the INSPIRE-ICOPE-CARE program
towards healthy aging. It includes "intrinsic capacity", defined as "the composite of all the
physical and mental capacities of an individual", which has a positive value towards
prevention, and is constructed by five domains: cognition, vitality/nutrition, sensory,
psychology, and mobility. ICOPE App and ICOPE Monitor are applications for the
self-assessment and monitoring of intrinsic capacity.
Hypothesis: Intrinsic capacity self-assessed by the ICOPE Apps could be associated with the
incidence of frailty and health outcomes. ICOPE Apps might support geriatric and primary care
during the COVID-19 pandemic and beyond.
Objectives: To assess the association between intrinsic capacity measured by the ICOPE Apps
at baseline and the incidence of frailty in community-dwelling older adults during 1-year
follow-up. Secondarily, to assess the association of intrinsic capacity and pre-frailty,
falls, functional decline, institutionalization, and mortality (COVID-19-related/not
related).
Methods: Protocol for a cohort study of community-dwelling adults ≥65-year-old, with no other
exclusion criteria than the inability to use the Apps or communicate by telephone/video-call
for any reason (cognitive or limited access to telephone/video-call). Intrinsic capacity
measured by the ICOPE Apps and Rockwood's clinical frailty scale will be assessed at
baseline, 4-, 8- and 12-month follow-up by telephone/video-call. Assuming a prevalence of
frailty of 10.7%, and incidence of 13% (alpha-risk=0.05), 400 participants at 12-month
end-point (relative precision=0.10) and 600 participants at baseline will be required.
Associations among the decrease in intrinsic capacity, incidence of frailty, and occurrence
of health adverse outcomes during 1-year follow-up are expected. ICOPE Apps might identify
individuals at higher risk of frailty and health adverse consequences. The implementation of
the ICOPE Apps into clinical practice might help to bring the practitioners closer to their
patients, deliver efficient person-centered care-plans, and benefit the healthcare systems
during the COVID-19 pandemic and beyond.
Description:
INTRODUCTION The World Health Organization aims at promoting initiatives focused on the
preservation of individuals' physical and mental capacities to achieve older ages in a good
health status (Healthy Aging). The INSPIRE Integrated Care for Older People (ICOPE)-CARE is
an European program for healthy aging and geroscience research developed by the WHO and
coordinated by Gérontopôle of Toulouse (France) in the Occitania Region since 2019. The
INSPIRE ICOPE-CARE program will provide evidence about trajectories of life (Normograms for
Healthy Ageing Standards), going from animal models to humans and the healthcare systems. As
a second step, the French government is aligned with the strategy of WHO 2020-2030 for the
continuity of this line of research (https://www.who.int/ageing/en/) and the French
Presidential Plan Grand Age has scheduled the implementation of the program INSPIRE
ICOPE-CARE in France. This is aligned with other European national healthcare plans, where
the implementation of new technologies is considered as an efficient resource to improve
patients' health.
INSPIRE ICOPE-CARE includes the assessment of "intrinsic capacity", a new term launched in
the WHO in the plan of action 2016-2020. The operational definition of "intrinsic capacity"
is "the composite of all the physical and mental capacities of an individual" and is
constructed by 5 domains: locomotion, vitality, sensory (vision and hearing), cognition, and
psychological domain. Intrinsic capacity has a positive values focusing on disease
prevention, and influencing the viewpoint from a negative paradigm of ageing (diseases,
disability, frailty, etc.) towards the positive focus of a "healthy aging".
The INSPIRE ICOPE-CARE program involves the self-assessment of intrinsic capacity by new
technologies. Indeed, the ICOPE application (App) is self-administered for the screening of
intrinsic capacity, and, the ICOPE Monitor is aimed on the diagnosis and 4-month monitoring
of intrinsic capacity. The two Apps, already in use as part of the INSPIRE ICOPE-CARE
program, are available free-of-charge in Apple or Android Store. Frailty, defined as a
"syndrome characterized by a clinical state in which there is an increase in an individual's
vulnerability for developing an increased dependency and/or mortality when exposed to a
stressor", is also a construct of several domains. However, there are wide differences among
frailty and intrinsic capacity, i.e. frailty is driven by deficits, while intrinsic capacity
is driven by reserves; frailty is an approach towards treatment usually measured in clinical
settings, while intrinsic capacity is a preventive approach focused on the community setting;
frailty has wide evidence about its prognosis capacity, while intrinsic capacity is quite
new; and finally, frailty assessment requires the administration of comprehensive geriatric
assessment by a healthcare professional, while intrinsic capacity could be self-assessed. It
would be expected that intrinsic capacity, measured by the Apps is associated to frailty, but
this association remains unexplored.
The onset of the COVID-19 pandemic due to a novel coronavirus (SARS-CoV-2) in December 2019
has drastically change the world and clinical practice. Older patients are one of the
populations most affected by COVID-19, with a mortality rate of 8% in patients
70-79-year-old, 14.8% in those aged ≥80 years, and higher mortality in frail older
individuals, as frailty increases probability of all-cause mortality and death by infectious
diseases. The limited availability of primary care resources and the cancellation/delay of
visits in outpatients' clinics is hindering the control of chronic diseases, and increases
the risk of acute decompensation of chronic diseases in the short and medium term. These
patients would lose their health status and become frail, entering in the so called new
"COVID Spiraling Frailty Syndrome". Despite healthy general population is finishing
quarantine since May 2020, it is still unclear the duration of the isolation measures in
safety conditions in older population, particularly in presence of frailty. It seems timely
to unleash the potential of academic discoveries to help older people to maintain a good
health status and survive.
The investigators hypothesize that intrinsic capacity, self-assessed by the ICOPE App and
Monitor at baseline, could identify individuals at higher risk of developing frailty and
health adverse outcomes during 1-year follow-up. If these hypotheses are confirmed, ICOPE
Apps could be incorporated into clinical practice during the pandemic of COVID-19 and beyond.
OBJECTIVES The primary objective is to assess the relationship between intrinsic capacity
assessed with the ICOPE Apps (ICOPE App and ICOPE Monitor) at baseline and the incidence of
frailty in community-dwelling older adults during 1-year follow up. Secondarily, the
association between intrinsic capacity measured by the ICOPE Apps at baseline and the risk of
1-year mortality (COVID-19-related or not), pre-frailty, falls, functional decline,
institutionalization, and loss of quality of life in this population during 1-year follow-up
will be assessed.
METHODS Design Protocol for a prospective cohort study, designed to determine the incidence
of frailty in community-dwelling older people during 1-year follow-up, starting the
recruitment at a certain point of the COVID-19 pandemic and beyond. The Strengthening the
Reporting of Observational Studies in Epidemiology (STROBE) statement will be followed.
Subjects who volunteer and meet eligibility criteria will be consecutively included.
Settings Volunteers will be recruited from 1) the Geriatric Department, 2) Outpatient clinics
of primary care, and 3) Local press, television, and radio advertisements. In the first two
options, the clinicians in the Geriatrics or primary care department that collaborate with
the study, would identify a potential candidate and send an electronic mail with contact
details to the personal from the study. In the third option, volunteers will receive
instructions to proactively contact by telephone or electronic mail (e-mail) with the
personal from the study. After receiving the e-mails, a telephone or video-call between the
volunteer and the personal from the study will be scheduled in a maximum of 1 week. During
the first interview, subjects will be assessed for eligibility, receive detailed information
about the study, and sign the informed consent. Technical assistance in downloading the two
Apps, signing the informed consent, the baseline assessment, and schedule next follow-up will
be given during the first interview. The 4-, 8-, and 12-month follow-up will be conducted in
a similar way. The Geriatric and primary care Department count with the technical devices and
facilities to conduct the proposed test, and the Apps are free-of-charge (Apple /Android
Store https://www.youtube.com/watch?v=gLva4ReV9KA). Data will be analysed at the Research
Unit in Biostatistics, Public Health Department, University of Liege, Belgium. Table 1
summarizes study settings, variables, and timeline of the study.
Population Prospective cohort study of community-dwelling adults ≥65-year-old living at home,
with no other exclusion criteria than the inability to use the ICOPE Apps or communicate by
telephone/video-call for any reason (cognitive or limited access to technologies like
telephone/video-call).
Intrinsic capacity assessment Will be administered by the two Apps, screening by the ICOPE
App and diagnosis and monitoring by ICOPE Monitor.
Screening by the ICOPE App: The screening includes polar questions (yes/no) about the 5
domains of intrinsic capacity. Two results are possible: positive (probable decrease in
intrinsic capacity) or negative (intrinsic capacity not decreased). The App includes
possibility to record the summary of the screening, download it in pdf, or send it by mail.
Diagnosis and monitoring by the ICOPE Monitor: ICOPE Monitor includes identification and
informed consent of both the professional and the participant, detailed intrinsic capacity
assessment of the 5 domains. The results obtained in the 5 domains are provided as a
checklist ("right" or "wrong" in each domain). Updated advice for each domain and a link for
further information is also provided. The App automatically schedules the date for the next
4-month follow-up and sends the informed consent by mail to the volunteer.
Outcome measures Primary outcome measure: Incidence of frailty assessed by Rockwood's
clinical frailty scale (CFS) will be assessed at 12-month follow-up by telephone/video-call.
An score <4 will indicate robustness, 4-6 pre-frailty status, and ≥ 6 frailty. Secondary
outcome measures: Death (cause, COVID-19-related or not, and date), incidence of pre-frailty,
falls (number and date), functional decline (≥20 points in Barthel index),
institutionalization (date), and quality of life (EuroQol) at 12-month follow-up by a
telephone/video-call with the volunteer or a contact person.
Mortality Cause (COVID-19-related or not) and date of death will be recorded, reported by the
contact person if the participant did not respond to the scheduled follow-up. Gagne
comorbidity score and Walter index will be recorded at baseline and 12-month follow-up by
telephone/video call. Recent serum albumin levels required to fulfill the Walter index will
be provided by the geriatric and primary care physicians.
Falls Number and date) will be recorded by the volunteers on a personal dairy book.
Functional decline It will be defined by a decrease in ≥20 points of Barthel index. Barthel
index will be administered by telephone/video call at baseline and12-month follow-up.
Quality of life It will be measured by self-reported EuroQol (ranging from 0 -the worst
possible health status- to 1 -the best possible health status-) by telephone/video-call at
baseline and 12-month follow-up.
Covariate data collection Demographic and clinical data will be collected during the
telephone/video calls and used as covariates. Instrumental activities of daily living (IADL)
(maximum score 8 points). The ratio of the total score obtained / total score of the
applicable items will be used to avoid any discrimination based on usual housework
distribution among couple. E.g. if one of the members of a couple does not usually perform an
activity, that item will not account for that individual, then, the total score of the
applicable items will be 7 instead of 8.
Feasibility of the ICOPE App and ICOPE Monitor Feasibility will be defined as "the state or
degree of being easily or conveniently done" and explored by the Technological, Economical,
Legal, Operational, Schedule (TELOS)-feasibility score, which assesses the potential of
implementation of new systems, and considers them feasible if TELOS-feasibility score ≥3). It
will be administered to the geriatric and primary care practitioners who collaborate with the
study.
Sample size calculation Sample size has been calculated in terms of the ICOPE study primary
objective: to identify incidence of frailty in community-dwelling older patients. Table 2
shows the sample size calculation determined by a power calculation based on the width of the
confidence interval for a proportion and on the estimation of an incidence rate. Assuming a
prevalence of frailty of 10.7%, an incidence of 13% with an alpha risk of 0.05, the
investigators estimated that 400 participants at the 12-month end-point of the study would be
necessary to meet a degree of certainness regarding the incidence (relative precision of
0.10) meaning a sample of 600 volunteers at baseline should be cover a potential large
dropout regarding the characteristics of this study (observational, 1-year follow-up,
potential frail people, unknown adherence rate to the follow-up).
Statistical plan Descriptive analysis will be performed for each variable of the study.
Qualitative variables will be described by absolute numbers and relative frequencies (%).
Quantitative variables will be summarized by the use of means and standard deviation (SD) for
symmetrical distribution or median and the interquartile deviation for asymmetrical
distributions. Normality of variables will be checked graphically with histograms and
quantile-quantile plots, and tested by the Shapiro-Wilk test. A logarithmic transformation of
the data might be performed, if needed. The association between intrinsic capacity and the
outcomes measured during 1 year (frailty, autonomy decline, falls, hospitalization,
institutionalization, and death) will be studied by a binary logistic regression for binary
outcomes, by a multinomial logistic regression for the qualitative outcomes and by multiple
regression for quantitative outcomes. For logistic regressions, Odds ratio and 95% confidence
interval (CI) will be obtained.
The evolution of intrinsic capacity during the 1-year follow-up will be analyzed by
Generalized Linear Mixte Model (GLMM). These models will be also used to study the
association between intrinsic capacity and vital prognosis. Kaplan-Meier methods and Cox
proportional hazard model will be use to include the notion of time occurrence of frailty.
Finally, the association between survival and intrinsic capacity will be analyzed by a joint
model; the same analysis might be performed for other variables of interest, if required.
Multiple imputations methods would be applied to deal with missing data. The data will be
processed using SAS 9.4 (©SAS Institute Inc., Cary, NC, USA) and R (version 3.5) (R Core
Team) software packages. The level of statistical significance will be set as α = 5% (p <
0.05).
Ethics National and International research Ethics guidelines will be followed, including the
1964 Declaration of Helsinki and its further amendments, and the Committee on Publication
Ethics (COPE) guidelines. Data will be treated according to the law of data protection in
Belgium and the Regulation (EU) 2016/679 of the European Parliament and of the Council of 27
April 2016 on the protection of natural persons with regard to the processing of personal
data. The approval of the Ethics Committee (Comité d'Ethique Hospitalo-Facultaire
Universitaire de Liège) will be obtained. Written and oral information will be provided and
informed consent will be signed by all participants. The study has been registered at
www.clinicaltrials.gov on May, 2020).
Our study will determine the associations among decrease in intrinsic capacity, incidence of
frailty, and occurrence of health adverse outcomes in community-dwelling older people during
1-year follow-up, in the COVID-19 pandemic and beyond. If these associations are observed in
the study, the ICOPE Apps would be ready to be implemented in daily practice, following the
experience of the INSPIRE ICOPE-CARE in France (NCT04224038).
Several aspects of the study should be highlighted. First, it will include intrinsic capacity
assessment. Indeed, even if the association of intrinsic capacity with mortality, functional
decline, and falls was recently shown in older people in nursing homes, there is still very
few data in community-dwelling population. The rationale to select intrinsic capacity,
instead of using other syndromes or diseases, for example, sarcopenia, malnutrition, or
dementia, is due to the multidimensional characteristics of older people, which require a
global assessment. A single point of view might not be complete enough to take complex
decisions in clinical practice.
Second, the study will provide evidence about the relationship between intrinsic capacity and
frailty, which is a different multidimensional construct. Mortality has been selected as
clinically meaningful outcome of the study, as recommended by the Common data elements (CDE)
and core outcome measures (COMs) in Frailty research consensus and the Physical Frailty:
ICFSR International Clinical Practice Guidelines for Identification and Management. Frailty
has shown association with 2-fold higher all-cause mortality (HR 2.17, 95%CI 1.90-2.48),
including infectious diseases (HR 1.79, 95%CI 1.03-3.11). Sample size calculation was based
on a prevalence of frailty of 10.7% and incidence 13%. Despite lower incidence rates (3.9%,
8%), have been shown in other large cohorts, the highest one was selected for our sample size
calculation, due to the high probability of developing frailty during the pandemic ("COVID
Spiraling Frailty Syndrome"). Providing data about the relationship between intrinsic
capacity and frailty will pave the path towards the change in the negative paradigm of aging,
and a person-centred model focused on prevention and Healthy Aging.
Third, our study will include the use of new technologies by older people, which is an
emerging field with promising results. Several projects on the use of technologies to support
health status of older people are currently ongoing, e.g. the J48 supervised machine learning
algorithm is identifies future fallers among otherwise healthy, independent older adults;
eMIND is a randomized controlled trial that includes web-based multidomain interventions; and
the ALLEGRO living lab is an experimental hospital-based room for the testing of devices by
frail hospitalized older people. The International Network of Agencies for Health Technology
Assessment (INAHTA) provides high quality evidence about new technologies to help health care
suppliers and policy makers in their decisions. The Belgian Health Care Knowledge Centre
(KCE) has recently joined the INAHTA in 2020, which might be promising for this line of
research.
Finally, some limitations related to the cohort design should be acknowledged. The inclusion
of healthy community-dwelling older volunteers will be considered as a selection bias, as it
has been previously reported in other cohorts of community-dwelling older people. The
characteristics of voluntary older participants (motivation, involvement in self-care
management, etc.) might differ from those who refused to get involved in a research study.
Moreover, volunteers who are able to use online resources might be relatively younger at
baseline, and their health status might be better than the population of the same age. This
relatively healthy overall status expected at baseline will be a strength of our study, as
the findings will have higher external validity for general population.
In summary, this study will apply the "Action-research philosophy" to bridge the gap between
research and clinical practice. It will provide evidence to implement the ICOPE App and ICOPE
Monitor, deliver efficient person-centered care-plans, and benefit older adults,
professionals, and the healthcare systems during the COVID-19 pandemic and beyond.
Funding No funding has received to conduct this research.
