Tackling Disruptions to Frailty Interventions: Developing Personalized Interventions Targeted for Older Persons With Cardiac Frailty

Study Overview
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Brief Summary
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Background: Muscle mass loss and metabolic dysfunction, exacerbated by inactivity and nutritional inadequacies, underpin both cardiovascular disease and frailty in ageing. The investigators' proposal seeks to develop interventions in exercise and diet that are targeted for older adults with cardiac frailty. Methods: The investigators' proposal is a five-year study comprising of first phase (first 2-2.5 years) and second phase (next 2-2.5 years). In the first phase cardiac frail participants (up to N=500) from each healthcare transition (inpatient hospital, step-down community hospital, outpatient clinic/community) will be randomized to receive Intervention Sets or usual care. The second phase will scale up these programs. Three Intervention Sets A, B, and C will be implemented in the outpatient, step-down community hospital, and acute hospital settings. Diet intervention comprises meal sets prepared with nutrients involved in energy metabolism. Exercise training is facilitated by hospital gyms and hospital physiotherapists. Diet and exercise behavior will be monitored using questionnaires, video conferencing and meal photos. Significance: Clinical studies are urgently needed using consistent frailty tools to evaluate the efficacy and promise of frailty interventions, targeted to achieve reversal/retardation of frailty. When scaled up, these approaches will provide high-quality science needed to manage cardiac frailty towards healthier population ageing.

Detailed Description
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BACKGROUND Cardiovascular disease is a formidable disruptor of interventions related to exercise intervention. Patients and physicians face uncertainty about dispensing safe and effective exercise programs to frail patients with concomitant cardiovascular disease. This hesitancy permeates across transitions from acute to step-down care to community settings. Uncertainties include fear of exacerbating heart conditions, individual variability in exercise response and what exercise targets to reach that is rational for each patient. Often, little or no exercise intervention is applied in the acute to step-down phases, which are the periods most critical for frailty reversal. Current dietary interventions do not address the special nutritional needs of acute cardiovascular conditions like heart failure, and may paradoxically induce a syndrome of cardiac cachexia that contributes to the downward spiral of frailty. STUDY DESIGN: This will be a prospective randomized clinical trial. The investigators' proposal is a five-year study comprising of first phase (first 2-2.5 years) and second phase (next 2-2.5 years). In the first phase cardiac frail participants (up to N=500) from each healthcare transition (inpatient hospital, step-down community hospital, outpatient clinic/community) will be randomized to receive Intervention Sets or usual care. The second phase will scale up these programs. At enrolment, pre-defined study time points and end of study, participants will undergo assessments of clinical status, frailty status, cardiovascular function, nutrition, quality of life (QOL), diet/exercise behaviour, and biospecimen sampling. Three Intervention Sets will be implemented in the outpatient, step-down community hospital, and acute hospital settings. Diet intervention comprises meal sets prepared with nutrients involved in energy metabolism. During the trial, exercise intervention is performed in hospitals and community hospitals by physiotherapists. Associated factors such as dietary, comorbidities and other related habits will be tracked simultaneously during the trial Intervention Set A: exercise sessions and meals over approximately 12 weeks. Intervention Set B : exercise sessions and meals over approximately 3 weeks. Intervention Set C: meals over approximately 3 weeks. PROCEDURES Baseline Procedures i. Cardiovascular measurements Non-invasive brachial blood pressure machine Echocardiography Electrocardiography ii. Biospecimen collection iii. Six-minute walk test iv. Musculoskeletal Analysis v. Cardiopulmonary exercise test (CPET)/ Treadmill vi. Questionnaires vii. Timed up and go (TUG) test Post-intervention procedures i. Cardiovascular measurements Non-invasive brachial blood pressure machine Echocardiography Electrocardiography ii. Biospecimen collection iii. Six-minute walk test iv. Musculoskeletal Analysis v. Questionnaires vi. Timed up and go (TUG) test Closing questionnaires

Official Title
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Tackling Disruptions to Frailty Interventions: Developing Personalized Interventions Targeted for Older Persons With Cardiac Frailty

Conditions
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Cardiovascular Diseases

Intervention / Treatment
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* Other: Intervention Set A
* Other: Intervention Set B
* Other: Intervention Set C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 21 years old Outdoor ambulant Exclusion Criteria: Bed-bound Dementia (Stage 6 onwards) Residing in sheltered or nursing home Cancer (to avoid confounding with cardiac disease sequelae from cancer) Participation in ongoing clinical trials that involve interventional drugs or devices Uncontrolled hypertension (systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥90mmHg) despite being on treatment for hypertension Low blood pressure (systolic blood pressure <90mmHg or diastolic blood pressure <40mmHg) Uncontrolled atrial fibrillation (controlled atrial fibrillation is allowed) Ventricular arrhythmias (such as ventricular tachycardia) Renal failure on dialysis Chronic kidney disease Stage 4 and above Nephrotic syndrome Liver cirrhosis Child's B and above Inflammatory Bowel Disease Severe uncontrolled gout Poorly controlled Diabetes Hba1c ≥9% On warfarin Presence of food allergies (such as shell-fish, prawn) Patient's life expectancy is expected to be less than one year at the time of potential enrolment as assessed by the investigator Nasogastric or parenteral nutrition Hypertrophic cardiomyopathy Cardiac amyloidosis Cardiac sarcoidosis

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Set A comprises of outpatient clinic/ community participants, who will be randomized in a 1:1 ratio into Group A1 (receiving Intervention Set A- exercise sessions and meals over approximately 12 weeks) or Group A2 (control/ usual care) Set B comprises of step-down community hospital participants, who will be randomized in a 1:1 ratio into Group B1 (receiving Intervention Set B- exercise sessions and meals over approximately 3 weeks) or Group B2 (control/ usual care) Set C comprises of acute community hospital participants, who will be randomized in a 1:1 ratio into Group C1 (receiving Intervention Set C- meals over approximately 3 weeks) or Group C2 (control/ usual care)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Outpatient clinic/community participants receiving exercise sessions and meals (A1)<br>Outpatient clinic/community participants receiving intervention Set A (exercise sessions and meals over approximately 12 weeks) | Other: Intervention Set A<br>* exercise sessions and meals over approximately 12 weeks<br>|
| No Intervention: Outpatient clinic/community participants receiving control/usual care (A2)<br>Outpatient clinic/community participants receiving control/usual care | |
| Experimental: Step-down community hospital participants receiving exercise sessions and meals (B1)<br>Step-down community hospital participants receiving Intervention Set B (exercise sessions and meals over approximately 3 weeks) | Other: Intervention Set B<br>* exercise sessions and meals over approximately 3 weeks<br>|
| No Intervention: Step-down community hospital participants receiving control/usual care (B2)<br>Step-down community hospital participants receiving control/usual care | |
| Experimental: Acute hospital participants receiving meals (C1)<br>Acute hospital participants receiving Intervention Set C (meals over approximately 3 weeks) | Other: Intervention Set C<br>* meals over approximately 3 weeks<br>|
| No Intervention: Acute hospital participants receiving control/usual care (C2)<br>Acute hospital participants receiving control/usual care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in cardiovascular markers | Change in cardiovascular variables are diastolic function variables such as mitral annular velocities (m/s) OR; Change in Aerobic capacity (V02, ml/kg/min) | at 14 weeks from baseline | 
| Improvement in skeletal muscle | Change in skeletal muscle mass (grams) | at 14 weeks from baseline | 
| Improvement in Fried Frailty Phenotype Score (improvement in any domain) (i.e., reduction in score) |  | at six months from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in metabolite level | Any change in metabolite (microM) | Three months and six months from baseline | 
| Improvement in Quality of life (QOL): EuroQOL-5D-5L (higher score) | A unit increase (i.e., improvement) in QOL score | Three months and six months from baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Frailty, Intervention, Cardiac Frailty Interventions