A Randomised, Controlled Trial of a Low-energy Diet for Improving Functional Status in Heart Failure With PRESERVED Ejection Fraction Preserved Ejection Fraction (AMEND)

University of Leicester

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Heart Failure, Diastolic; Diabetes Mellitus Type 2 in Obese; Heart Failure With Preserved Ejection Fraction; Diabetes Mellitus, Type 2; Obesity Adult Onset

Treatments: Diagnostic Test: Accelerometery; Other: Assessment of sarcopenia; Diagnostic Test: Blood test; Other: Assessment of quality of life and heart failure symptoms; Diagnostic Test: Transthoracic echocardiography; Diagnostic Test: 6 minute walk test (6MWT); Other: Assessment of frailty; Diagnostic Test: Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy; Diagnostic Test: Electrocardiogram; Drug: Low calorie meal replacement plan; Diagnostic Test: Skeletal muscle strength using handgrip strength and quadriceps (Cybex dynamometer); Other: Qualitative interview

Study type: Interventional

Funder types: Other

Identifiers

NCT05887271

0861

Details and patient eligibility

About

Heart failure with preserved ejection fraction (HFpEF) is a common and serious complication of obesity and type 2 diabetes (T2D). HFpEF occurs when the heart muscle unable to relax efficiently to pump the blood around the body. This leads to fluid build-up, breathlessness and inability to tolerate physical exertion. People who develop HFpEF do less well because treatment options are limited. Pilot data in patients with obesity and diabetes and a small number of patients with HFpEF have shown improvements in exercise capacity and reversal of changes in the heart and blood vessels. This study will assess if this is achievable in a multi-ethnic cohort of patients with established HFpEF. A total of 63 adults will be invited and allocate by chance into two groups: 1) 12-weeks of a low calorie diet or 2) Standard care and health advice on how to lose weight followed by the option to have the low calorie diet after 12-weeks. The study will determine if weight loss over 12 weeks can improve heart function, symptoms and ability to exercise. Additionally, participants' views on changing their diet and how this has impacted their symptoms will be sought during the study in an optional interview. This will help guide treatments planning in the future to get maximum benefits, and to individualize support to patients from different cultural backgrounds.

Full description

Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogenous syndrome, typified by severe exercise intolerance and with limited treatment options. Weight loss achieved through a low energy meal-replacement plan (MRP) has been shown to lead to reversal of cardiovascular remodelling in ethnically diverse asymptomatic adults with pre-HFpEF and HFpEF. This trial will translate this experience with the pragmatic low energy MRP into a symptomatic, multi-ethnic cohort of obese HFpEF, across four sites (Leicester, Manchester, Leeds and Oxford) to assess its efficacy in improving exercise intolerance, symptoms, quality of life, cardiovascular remodelling, and skeletal myopathy.

Enrollment: 63 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Established clinical diagnosis of heart failure with preserved ejection fraction HFpEF (EF>45%) made by a cardiologist or a primary care physician with heart failure expertise, or a heart failure nurse
2. Clinically stable for ≥ 3 months (no admissions to hospital)
3. Obesity (BMI ≥30kg/m2 if white European or ≥27kg/m2 if Asian, Middle Eastern or Black ethnicity)
4. Age ≥18

Exclusion criteria

1. Inability to walk/undertake 6-minute walk test
2. Inability to follow a low-energy MRP
3. HFpEF due to infiltrative cardiomyopathy (cardiac amyloidosis or sarcoidosis), genetic hypertrophic cardiomyopathy, restrictive cardiomyopathy/pericardial disease or congenital heart disease.
4. Recovered EF (previous EF < 40%) unless reduced EF was in context of tachycardia induced cardiomyopathy (eg AF/Aflutter).
5. Known heritable, idiopathic or drug-induced pulmonary arterial hypertension
6. Severe chronic obstructive pulmonary disease (FEV1< 1.0L)
7. Severe primary valvular heart disease
8. Anaemia (Hb<100g/L)
9. Severe renal disease (eGFR < 30 ml/min/1.73 m2)
10. Weight loss > 5kg in preceding 3 months.
11. Symptomatic gallstones (including biliary colic) or cholecystitis within last 3 months
12. Active substance abuse (drugs or alcohol)
13. History of bariatric surgery in the last 3 years
14. Active illness likely to cause change in weight
15. Women who are pregnant or are considering pregnancy
16. People currently participating in another clinical research trial that is likely to affect diet or weight change.
17. History of a severe mental illness including an eating disorder

17. Individuals with a diagnosis of Type 1 diabetes mellitus.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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63 participants in 2 patient groups

Low calorie meal replacement plan (MRP) arm

Experimental group

Description:

The MRP comprises of 3-4 meals a day (850kcal/day) supplied by Counterweight. Participants will be supported by professional research dieticians, and a study clinician. Participant health and medications will be monitored throughout the study. Offered to the comparator arm after 12 weeks as a control participant.

Treatment:

Other: Assessment of frailty

Other: Qualitative interview

Diagnostic Test: 6 minute walk test (6MWT)

Diagnostic Test: Transthoracic echocardiography

Diagnostic Test: Skeletal muscle strength using handgrip strength and quadriceps (Cybex dynamometer)

Other: Assessment of quality of life and heart failure symptoms

Diagnostic Test: Blood test

Other: Assessment of sarcopenia

Diagnostic Test: Electrocardiogram

Drug: Low calorie meal replacement plan

Diagnostic Test: Accelerometery

Diagnostic Test: Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy

Wait list control arm: Guideline driven care with attention control arm followed by optional MRP

Active Comparator group

Description:

Dietary advice to participants will be given in line with NICE guidelines for cardiovascular risk modification. Heart failure specific advice on exercise will be given in line with guidelines. After 12 weeks as a control participant, these individuals will then have the option to receive the meal replacement plan and repeat assessments after a further 12 weeks.

Treatment:

Other: Assessment of frailty

Other: Qualitative interview

Diagnostic Test: 6 minute walk test (6MWT)

Diagnostic Test: Transthoracic echocardiography

Diagnostic Test: Skeletal muscle strength using handgrip strength and quadriceps (Cybex dynamometer)

Other: Assessment of quality of life and heart failure symptoms

Diagnostic Test: Blood test

Other: Assessment of sarcopenia

Diagnostic Test: Electrocardiogram

Drug: Low calorie meal replacement plan

Diagnostic Test: Accelerometery

Diagnostic Test: Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy