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

June 3, 2025 updated by: National Heart Centre Singapore

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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

  1. 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

  2. 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
  3. Closing questionnaires

Study Type

Interventional

Enrollment (Estimated)

500

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Singapore
      • Singapore, Singapore, 169609
      • Singapore, Singapore, 529889
        • Recruiting
        • Changi General Hospital
        • Contact:
          • Chun How Ooi
      • Singapore, Singapore, 544886
        • Recruiting
        • Sengkang General Hospital
        • Contact:
          • Zijuan Huang
      • Singapore, Singapore, 609606
        • Recruiting
        • Jurong Community Hospital
        • Contact:
          • Alvin Ong
      • Singapore, Singapore, 159964
        • Recruiting
        • Alexandra Hospital
        • Contact:
          • Laureen Yi-Ting Wang
      • Singapore, Singapore
        • Recruiting
        • NHG Polyclinics
        • Contact:
          • Shu Yun Tan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 21 years old
  • Outdoor ambulant

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement in cardiovascular markers
Time Frame: at 14 weeks from baseline
  • 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
Time Frame: at 14 weeks from baseline
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)
Time Frame: at six months from baseline
at six months from baseline

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants who experience a major adverse cardiovascular events
Time Frame: Thirty-six (36) months from baseline
Include cardiac mortality, acute myocardial infarction, unstable angina, any revascularization, heart failure, atrial fibrillation, strokes
Thirty-six (36) months from baseline
Other events include proportion of participants who experience : death, falls, fractures, hospitalization for any cause, admission into nursing home
Time Frame: Thirty-six (36) months from baseline
Thirty-six (36) months from baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Heart Centre Singapore

Investigators

  • Principal Investigator: Angela Su-Mei Koh, MBBS, MPH, National Heart Centre Singapore

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 12, 2023

Primary Completion (Estimated)

June 21, 2028

Study Completion (Estimated)

June 21, 2028

Study Registration Dates

First Submitted

June 15, 2023

First Submitted That Met QC Criteria

July 6, 2023

First Posted (Actual)

July 14, 2023

Study Record Updates

Last Update Posted (Estimated)

June 5, 2025

Last Update Submitted That Met QC Criteria

June 3, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023/2086

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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