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

Cardiovascular Diseases Clinical Trial

— INDEPENDENCY  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05946174
• Other study ID #: 2023/2086
• Status: Recruiting
• Phase: N/A
• Start date: July 12, 2023
• Est. completion date: June 21, 2028

Study information

• Verified date: August 2023
• Source: National Heart Centre Singapore
• Contact: Angela Su-Mei Koh
• Phone: +65 6704 8961
• Email: angela.koh.s.m[@]singhealth.com.sg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: June 21, 2028
• Est. primary completion date: June 21, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Frailty

Intervention

Other:
• 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

Locations

Country	Name	City	State
Singapore	Alexandra Hospital	Singapore
Singapore	Changi General Hospital	Singapore
Singapore	Jurong Community Hospital	Singapore
Singapore	National Heart Centre Singapore	Singapore
Singapore	NHG Polyclinics	Singapore
Singapore	Sengkang General Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
National Heart Centre Singapore

Country where clinical trial is conducted

Singapore, 

References & Publications (4)

Keng BMH, Gao F, Teo LLY, Lim WS, Tan RS, Ruan W, Ewe SH, Koh WP, Koh AS. Associations between Skeletal Muscle and Myocardium in Aging: A Syndrome of "Cardio-Sarcopenia"? J Am Geriatr Soc. 2019 Dec;67(12):2568-2573. doi: 10.1111/jgs.16132. Epub 2019 Aug 16. — View Citation

Koh AS, Gao F, Leng S, Kovalik JP, Zhao X, Tan RS, Fridianto KT, Ching J, Chua SJ, Yuan JM, Koh WP, Zhong L. Dissecting Clinical and Metabolomics Associations of Left Atrial Phasic Function by Cardiac Magnetic Resonance Feature Tracking. Sci Rep. 2018 May 25;8(1):8138. doi: 10.1038/s41598-018-26456-8. — View Citation

Koh AS, Gao F, Liu J, Fridianto KT, Ching J, Tan RS, Wong JI, Chua SJ, Leng S, Zhong L, Keng BM, Huang FQ, Yuan JM, Koh WP, Kovalik JP. Metabolomic profile of arterial stiffness in aged adults. Diab Vasc Dis Res. 2018 Jan;15(1):74-80. doi: 10.1177/1479164117733627. Epub 2017 Oct 4. — View Citation

Koh AS, Gao F, Tan RS, Zhong L, Leng S, Zhao X, Fridianto KT, Ching J, Lee SY, Keng BMH, Yeo TJ, Tan SY, Tan HC, Lim CT, Koh WP, Kovalik JP. Metabolomic correlates of aerobic capacity among elderly adults. Clin Cardiol. 2018 Oct;41(10):1300-1307. doi: 10.1002/clc.23016. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of participants who experience a major adverse cardiovascular events	Include cardiac mortality, acute myocardial infarction, unstable angina, any revascularization, heart failure, atrial fibrillation, strokes	Thirty-six (36) months from baseline
Other	Other events include proportion of participants who experience : death, falls, fractures, hospitalization for any cause, admission into nursing home		Thirty-six (36) months from baseline
Primary	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
Primary	Improvement in skeletal muscle	Change in skeletal muscle mass (grams)	at 14 weeks from baseline
Primary	Improvement in Fried Frailty Phenotype Score (improvement in any domain) (i.e., reduction in score)		at six months from baseline
Secondary	Improvement in metabolite level	Any change in metabolite (microM)	Three months and six months from baseline
Secondary	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