Clinical trial NCT05946109: Effect of an Exercise Program for Frail Older Adults
Official title: Tackling FRAILTY: ACTIVE-AGE@home: a Home-based Functional Exercise Program for Community Dwelling Frail Older Adults Provided by Professionals and Volunteers.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Frailty
Keywords: older adults
physical activity
exercise
rehabilitation
occupational therapy
health promotion
goal-oriented care
home based
primary care
geriatrics
activities of daily living
meaningful activities
cognition
loneliness
cost-effectiveness
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
Collaborators: name: University Ghent
name: Universiteit Antwerpen
name: Odisee University college for applied sciences
name: Artevelde University of Applied Sciences
First posted: 2023-07-14
Enrollment: 195
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This project aims to investigate the effect on physical functioning, cognition, loneliness, self-management, subjective health and meaningful activities of frail older adults, provided by professionals (study condition 1) or provided by trained volunteers (study condition 2) or when not provided (controls, study condition 3). Since it is hypothesized that volunteers will reduce health care cost, the investigators will assess health care utilization in the three groups. Therefore, a RCT will be used.. The duration of the intervention is 24 weeks and assessments will be done before, after and at 48 weeks follow-up. The trial is designed in line with The Geriatric ICF Core Set reflecting health-related problems in community-living older adults aged 75 years and older without dementia. To limit possible bias due to non-specific treatment effects, all participants allocated to both intervention arms will receive an identical amount of treatment, securing balanced treatment arms.
Primary purpose: TREATMENT

Brief summary: Despite the high level of evidence for physical activity as a countermeasure for frailty, the current Flemish standard of care does not include structural PA interventions for community-dwelling frail older adults. One barrier for this, is the high cost of supervised physical activity programmes.

Therefore, in this pragmatic randomised controlled trial, the investigators will consider the Flemish current standard of care for frail older adults as a control group. Intervention condition 1 reflects the state-of-the-art physical activity intervention provided by professionals and intervention condition 2 consists of the same intervention provided by trained volunteers. It is hypothesized that the intervention in both intervention conditions will have significant effects on functional ability, cognition, loneliness, self-management, subjective health and meaningful activities and that it can alleviate the financial burden of condition 1 (cost-effectiveness). The pretrajectory of this study was based on the 'British Medical Research Council guidance' for the development and evaluation of complex interventions. This resulted in a comprehensive, state-of-the art personalised physical activity programme for community-dwelling frail older adults: ACTIVE-AGE@home. The programme adheres to current guidelines for physical activity and exercise for frail older adults and considers low threshold and meaningful activities for the participants. The latter perfectly aligns with the complex bio-psychosocial components of frailty. Positive results will help reduce negative outcomes of frailty in older adults and will also reduce health and social expenditures. This study aligns with a 'prevention and health promotion' model.

Detailed description: Studies show that physical activity can lower the risk of developing frailty and also reduce frailty-status once it is present. Favorable effects of physical activity on frail older adults include improved muscle strength, aerobic capacity, Quality of Life, cognition, and depression. There is also evidence of a dose response relationship between higher intensities of physical activity and lower levels of frailty. The current body of knowledge proves that physical activity interventions are the best possible (first-choice) treatment to tackle frailty. Despite of this, according to the World Health Organisation, only 7% of frail older adults meet the physical activity guidelines. In scientific literature and previously conducted own research several intrapersonal barriers were detected as a possible explanation for the low participation rates: fear, negative self-esteem, feeling useless, but also environmental barriers: lack of accessibility (location, information, ...) and the absence of a familiar and trustworthy trainers, informal caregivers or volunteers to support the older adults and provide motivation and follow-up.

Rationale for study design:

This study is developed considering the United Nation's 'Decade of Healthy Ageing' and Europe's research agenda on prevention. Therefore, this project fits perfectly with initiatives such as 'Ageing in Place' and 'Societalisation of care'. This project also aligns with the overall framework of the vision on Healthy Ageing of the World Health Organisation (WHO).

Both physical activity and home-based services are reported as part of the top 10 priorities for frailty research by the Canadian Frailty Priority Setting and was co-created with frail older adults. More specifically, RCTs (followed by cost effectiveness studies) focusing on interventions for older adults with frailty are a high priority for the frailty research agenda. Strategies to slow the progression of frailty or convers the frailty state are paramount.

Volunteering:

Incorporating volunteering to provide physical activity interventions may reduce costs. In the 'Policy Framework for Active Ageing', the WHO advises to support peer leaders and groups that promote regular, moderate physical activity for people as they age and to inform and educate people and professionals about the importance of staying active as one grows older. The 'Flemish Council of the Elderly' together with the 'Flemish Institute for Health Promotion and Prevention' specifically recommends to train nonprofessional volunteers to counter frailty in lonely older adults. Also, Luger and coleaugues conducted a proof-of-concept study and showed that physical training, which is administered by trained lay nonprofessional volunteers, is feasible and can help to tackle frailty in older persons living at home. The fact that functional results of training can be obtained at a lower cost by the efforts of volunteers holds a cost saving potential which the investigators will be able to study. In Flanders 1 out of 8 people is volunteering and during the COVID-19 crisis the willingness to help others has risen.

Cost-effectiveness:

In Europe estimates are that in 2018, 11% of older adults (\>65 years) were considered frail. Calculated for the whole EU-28 this means that a total of 56.364.000 older adults were frail. According to the 'Flemish Institute for Statistics' (the governing body where Flemish demographic data are collected and analyzed), the percentage of older adults in Flanders, aged 65 years or older, will increase from 20% or \>1.300.000 older adults in 2017 to 23% or \>1.500.000 older adults in 2027. Given the evidence based estimates that 35%-40% of older adults are in a reversible frail or pre-frail state, this means that the target population of this study has the magnitude of up to 600.000 Flemish older adults in 2027 that could benefit from ACTIVE-AGE@home. Regarding the societal and economic benefits, several studies pointed out that the average additional costs associated with frailty when controlled for ageing and multimorbidity range from 1.500 to 5.000 euro per person per year. As frailty is expected to be stabilized or reverted, a reduction in health care utilization by any intervention is realistic. The study by Sicsic demonstrated the impact of frailty transitions on health care utilisation. In their Europe-wide study, they found that becoming frail is associated with a 14.4 percentage point increase in hospital use, about 2 percentage points in GP consultations and 7.7 percentage point increase in specialist care. A delay or reverse of frailty clearly shows the cost saving potential of the intervention under study.

Study design:

The Proof of Concept Studies showed positive effects for the participants. Now, the research consortium will further evaluate ACTIVE-AGE@home for frail community-dwelling older adults, by testing its effect and evaluate also its cost-effectiveness when it is administered by professionals or by trained volunteers in combination with professionals and compare this to the care as usual in Flanders. A pragmatic RCT design is therefore the most relevant, effective, and efficient approach for this objective.

The duration of the intervention is 24 weeks and assessments will be done before (T=0), after (T=1) and at 48 weeks follow-up (T=2). To limit possible bias due to non-specific treatment effects, all participants allocated to the two intervention arms will receive an identical amount of treatment, securing balanced treatment arms. The third group will receive care as usual for frail older adults.

Condition 1: professionals The frail participants are visited three times a week by the trained professional, for 24 weeks with in total 72 sessions. Each session is 1 hour in duration. Thus, they receive 72 training hours equal to the volunteer-administered program. The professionals will receive three 4h training courses to gain more knowledge and practice regarding the specific innovative aspects of the programme, including information on frailty and ageing, motivational coaching, physical training principles and ACTIVE-AGE@home.

Condition 2: volunteers The frail participants are visited three times a week by trained non-professional volunteers, for 24 weeks with in total 72 sessions. Each session is 1 hour in duration. Thus, they receive 72 training hours, equal to the professional administered program. The volunteers will also receive three 4h training courses comparable to the professionals. Additionally, volunteers are coached by a professional during the intervention.

Condition 3: usual care / control Frail participants will receive no visits from volunteers or professionals and will not be trained with the ACTIVE-AGE@home exercise program. They can receive other care that is provided by health care professionals to frail older adults.

Health economic evaluations:

The health economic evaluations concern incremental analyses in terms of incremental costs over incremental effects between the alternatives. Therefore cost-utility analyses will be conducted. The thresholds suggested by the Belgian Health Care Knowledge Centre will be applied, and are based on the welfare of our country, expressed in GDP per capita (≈40,000€/QALY). This threshold represents a willingness-to-pay, as society, for one adjusted quality of life year gained. It creates however the illusion that there is a "hard" cut-off in determining interventions to be cost-effective or not. The latter calls for cautious interpretation of results as these cut-offs should be interpreted as indicative rather than a hard decision-rule. The investigators plan to conduct threshold analyses which look for a tipping point for one or more specific input parameters that lead to an incremental cost-effectiveness ratio above or below the threshold. Additionally, probabilistic sensitivity analyses will be conducted and presented in cost-effectiveness acceptability curves indicating at each possible threshold the likelihood whether one of the intervention arms is cost-effective compared to the alternative. This kind of analyses is informative to health decision policymakers in providing insight on factors that lead (or not) to a more cost-effective approach. These kinds of analyses will be presented to the advisory board for further discussion. Trial-based economic evaluation: first, the individual participant data from both groups will be used to estimate the health outcomes and costs of ACTIVE-AGE@home over the period from recruitment to 12 months. The cost-effectiveness analyses will be carried out from a societal perspective based on the Belgian guideline for health economic evaluations. The direct medical costs encompass all costs for treatment and follow-up from the health system perspective and all out-of-pocket contributions by the participant. National tariffs will be used for the valuation. Direct non-medical costs include transport costs, and home care help, whereas indirect costs include productivity loss due to informal care which will be documented and valued using the human capital approach and proxy good methods. The effects are expressed in utilities, derived from the national values of the MOS-SF-36. QALYs will be calculated using the area under the curve method. The cost-effectiveness of the intervention will be expressed in incremental cost per QALY gained (quality-adjusted life years). The incremental cost per QALY will be calculated as a ratio of (Expected Cost ACTIVE-AGE@home -Expected Cost standard care) / (Expected Outcome ACTIVEAGE@home - Expected Outcome standard care). The robustness of the results will be analyzed by probabilistic sensitivity analyses on the cost as well as on the outcome. Bootstrapping with replacement will be employed utilizing @Risk and MS Excel®, using a minimum of 1000 iterations to obtain 2.5% and 97.5% percentiles of the incremental cost-effectiveness ratio (ICER) distribution. All bootstrapped ICERs will be presented on a cost-effectiveness plane to determine the robustness of the ICER, and to determine the probability that ACTIVE-AGE@home is cost-effective at various willingness-to-pay thresholds. A cost-effectiveness acceptability curve will be used to depict the probabilities of acceptable ICERs.

Model based economic evaluation: In addition to the trial-based evaluation a model based evaluation will be performed which will allow us to account for the expected costs and health outcomes in both intervention and control groups beyond the follow-up period of the trial. A probabilistic Markov model will be developed compliant to the commonly used guidelines. The investigators assume a cycle of 1 year in the model and applying a lifetime horizon. Lifetime incremental costs and QALYs will be the input for the ICER calculation. Discount rates of 3% for costs and 1.5% for utilities will be applied, which is in line with the Belgian guidelines. Non-parametric bootstrapping will be applied for both costs and outcomes to test the robustness of the results. These iterations will be presented in cost-effectiveness planes. Probabilities to be cost effective for the different willingness-to-pay thresholds will be presented in cost-effectiveness acceptability curves.

Eligibility criteria: Inclusion Criteria:

* \>70 years adults
* Frail according to the frailty phenotype of Fried, defining frailty as the presence of 3 or more of the following 5 criteria: unintentional weight loss, weakness, exhaustion (low energy level), slowness (slow gait) and low physical activity

Exclusion Criteria:

life expectancy less than 12 months by any cause

* oncologic participants with active treatment
* treatment with exercise therapy in the preceding 6 months
* any contra-indication for exercise therapy as established by the treating physician/family practitioner
* cognitive impairment (unable to understand the test instructions and/or Mini Mental State Examination score \<23/30)
* unable to understand the Dutch language
* diagnosed with Parkinson or Multiple Sclerosis
* having had a stroke in the preceding 6 months" to the registry

Primary outcomes:
measure: The Timed Chair Stand (TCS)
timeFrame: T0 = 0 weeks, prior to start of exercise program
measure: The Timed Chair Stand (TCS)
timeFrame: T1 = 24 weeks, at the end of the exercise program
measure: The Timed Chair Stand (TCS)
timeFrame: T2 = 48 weeks, follow up measurement
Secondary outcomes:
measure: Two Minute Step Test (TMST)
timeFrame: T0 = 0 weeks, prior to start of exercise program
measure: Two Minute Step Test (TMST)
timeFrame: T1 = 24 weeks, at the end of the exercise program
measure: Two Minute Step Test (TMST)
timeFrame: T2 = 48 weeks, follow up measurement
measure: The Timed Up and Go Test
timeFrame: T0 = 0 weeks, prior to start of exercise program
measure: The Timed Up and Go Test
timeFrame: T1 = 24 weeks, at the end of the exercise program
measure: The Timed Up and Go Test
timeFrame: T2 = 48 weeks, follow up measurement
measure: MOS 36-item-short-form health survey (SF-36)
timeFrame: T0 = 0 weeks, prior to start of exercise program
measure: MOS 36-item-short-form health survey (SF-36)
timeFrame: T1 = 24 weeks, at the end of the exercise program
measure: MOS 36-item-short-form health survey (SF-36)
timeFrame: T2 = 48 weeks, follow up measurement
measure: iMTA Medical Consumption Questionnaire (iMCQ)
timeFrame: T0 = 0 weeks, prior to start of exercise program
measure: iMTA Medical Consumption Questionnaire (iMCQ)
timeFrame: T1 = 24 weeks, at the end of the exercise program
measure: iMTA Medical Consumption Questionnaire (iMCQ)
timeFrame: T2 = 48 weeks, follow up measurement
measure: MOCA Montreal Cognitive Assessment
timeFrame: T0 = 0 weeks, prior to start of exercise program
measure: MOCA Montreal Cognitive Assessment
timeFrame: T1 = 24 weeks, at the end of the exercise program
measure: MOCA Montreal Cognitive Assessment
timeFrame: T2 = 48 weeks, follow up measurement
measure: Trail making test
timeFrame: T0 = 0 weeks, prior to start of exercise program
measure: Trail making test
timeFrame: T1 = 24 weeks, at the end of the exercise program
measure: Trail making test
timeFrame: T2 = 48 weeks, follow up measurement
measure: Rey Auditory Verbal Learning Test
timeFrame: T0 = 0 weeks, prior to start of exercise program
measure: Rey Auditory Verbal Learning Test
timeFrame: T1 = 24 weeks, at the end of the exercise program
measure: Rey Auditory Verbal Learning Test
timeFrame: T2 = 48 weeks, follow up measurement
measure: De Jong Gierveld 11-item loneliness scale
timeFrame: T0 = 0 weeks, prior to start of exercise program
measure: De Jong Gierveld 11-item loneliness scale
timeFrame: T1 = 24 weeks, at the end of the exercise program
measure: De Jong Gierveld 11-item loneliness scale
timeFrame: T2 = 48 weeks, follow up measurement
measure: Engagement in meaningful activities scale
timeFrame: T0 = 0 weeks, prior to start of exercise program
measure: Engagement in meaningful activities scale
timeFrame: T1 = 24 weeks, at the end of the exercise program
measure: Engagement in meaningful activities scale
timeFrame: T2 = 48 weeks, follow up measurement
measure: Self-Management Abilities Scale - Short Form2
timeFrame: T0 = 0 weeks, prior to start of exercise program
measure: Self-Management Abilities Scale - Short Form2
timeFrame: T1 = 24 weeks, at the end of the exercise program
measure: Self-Management Abilities Scale - Short Form2
timeFrame: T2 = 48 weeks, follow up measurement
measure: Fatigue resistance grip strength test
timeFrame: T0 = 0 weeks, prior to start of exercise program
measure: Fatigue resistance grip strength test
timeFrame: T1 = 24 weeks, at the end of the exercise program
measure: Fatigue resistance grip strength test
timeFrame: T2 = 48 weeks, follow up measurement
measure: Activities of Daily Life (National Health Interview Survey) (HIS)
timeFrame: T0 = 0 weeks, prior to start of exercise program
measure: Activities of Daily Life (National Health Interview Survey) (HIS)
timeFrame: T1 = 24 weeks, at the end of the exercise program
measure: Activities of Daily Life (National Health Interview Survey) (HIS)
timeFrame: T2 = 48 weeks, follow up measurement
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: UZ Brussels
state: Brussel
Study officials:
affiliation: VUB
name: Patricia De Vriendt, Prof dr
role: PRINCIPAL_INVESTIGATOR
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