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

Phase 2

Recruiting

• Conditions: Heart Failure With Preserved Ejection Fraction; Diabetes Mellitus, Type 2; Diabetes Mellitus Type 2 in Obese; Heart Failure, Diastolic; Obesity Adult Onset
• Interventions: Drug: Low calorie meal replacement plan; Diagnostic Test: Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy; Diagnostic Test: Transthoracic echocardiography; Diagnostic Test: Blood test; Diagnostic Test: Electrocardiogram; Diagnostic Test: Accelerometery; Diagnostic Test: 6 minute walk test (6MWT); Diagnostic Test: Skeletal muscle strength using handgrip strength and quadriceps (Cybex dynamometer); Other: Assessment of quality of life and heart failure symptoms; Other: Assessment of sarcopenia; Other: Assessment of frailty; Other: Qualitative interview; Diagnostic Test: Skeletal muscle magnetic resonance spectroscopy

• Registration Number: NCT05887271
• Lead Sponsor: University of Leicester

Brief Summary

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 102 adults will be invited and allocate by chance into two groups: either a 12-week diet or health advice on how to lose weight. 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.

Detailed 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 three sites (Leicester, Manchester and Oxford) to assess its efficacy in improving exercise intolerance, symptoms, quality of life, cardiovascular remodelling, and skeletal myopathy.

Study Timeline

• Study First Submitted: 2023-05-02
• Study First Submitted QC: 2023-05-31
• Study First Posted: 2023-06-02
• Study Start: 2023-12-05
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-28
• Last Update Posted: 2024-10-30
• Primary Completion: 2025-06-01
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 102

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

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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 disease95
4. Known heritable, idiopathic or drug-induced pulmonary arterial hypertension
5. Severe chronic obstructive pulmonary disease (FEV1< 1.0L)
6. Severe primary valvular heart disease
7. Anaemia (Hb<100g/L)
8. Severe renal disease (eGFR < 30 ml/min/1.73 m2)
9. Weight loss > 5kg in preceding 3 months.
10. Known gallstones/previous biliary colic

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low calorie meal replacement plan (MRP) arm	Electrocardiogram	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.
Low calorie meal replacement plan (MRP) arm	Accelerometery	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.
Low calorie meal replacement plan (MRP) arm	6 minute walk test (6MWT)	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.
Low calorie meal replacement plan (MRP) arm	Low calorie meal replacement plan	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.
Low calorie meal replacement plan (MRP) arm	Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy	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.
Low calorie meal replacement plan (MRP) arm	Transthoracic echocardiography	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.
Low calorie meal replacement plan (MRP) arm	Blood test	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.
Low calorie meal replacement plan (MRP) arm	Skeletal muscle strength using handgrip strength and quadriceps (Cybex dynamometer)	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.
Low calorie meal replacement plan (MRP) arm	Assessment of quality of life and heart failure symptoms	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.
Low calorie meal replacement plan (MRP) arm	Assessment of sarcopenia	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.
Low calorie meal replacement plan (MRP) arm	Assessment of frailty	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.
Low calorie meal replacement plan (MRP) arm	Qualitative interview	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.
Low calorie meal replacement plan (MRP) arm	Skeletal muscle magnetic resonance spectroscopy	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.
Guideline driven care with attention control arm	Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy	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. Health advice will be reinforced at regular 4-weekly phone calls.
Guideline driven care with attention control arm	Transthoracic echocardiography	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. Health advice will be reinforced at regular 4-weekly phone calls.
Guideline driven care with attention control arm	Blood test	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. Health advice will be reinforced at regular 4-weekly phone calls.
Guideline driven care with attention control arm	Assessment of sarcopenia	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. Health advice will be reinforced at regular 4-weekly phone calls.
Guideline driven care with attention control arm	Electrocardiogram	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. Health advice will be reinforced at regular 4-weekly phone calls.
Guideline driven care with attention control arm	Accelerometery	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. Health advice will be reinforced at regular 4-weekly phone calls.
Guideline driven care with attention control arm	6 minute walk test (6MWT)	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. Health advice will be reinforced at regular 4-weekly phone calls.
Guideline driven care with attention control arm	Skeletal muscle strength using handgrip strength and quadriceps (Cybex dynamometer)	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. Health advice will be reinforced at regular 4-weekly phone calls.
Guideline driven care with attention control arm	Assessment of quality of life and heart failure symptoms	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. Health advice will be reinforced at regular 4-weekly phone calls.
Guideline driven care with attention control arm	Assessment of frailty	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. Health advice will be reinforced at regular 4-weekly phone calls.
Guideline driven care with attention control arm	Qualitative interview	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. Health advice will be reinforced at regular 4-weekly phone calls.
Guideline driven care with attention control arm	Skeletal muscle magnetic resonance spectroscopy	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. Health advice will be reinforced at regular 4-weekly phone calls.

Primary Outcome Measures

Name	Time	Method
Change in the distance walked during 6 minute walk test (6MWT)	Assessed at baseline and 12 weeks, optional repeat at 24 weeks	The primary outcome measure is a change in the distance walked on 6MWT measured in meters

Secondary Outcome Measures

Name	Time	Method
Beneficial reverse cardiovascular remodelling	Assessed at baseline and 12 weeks, optional repeat at 24 weeks	CMR-derived measures of cardiovascular remodelling defined as left ventricular mass/volume ratio
Change in physical activity levels	Assessed at baseline and 12 weeks, optional repeat at 24 weeks	Improvement in physical activity will be determined by change in daily activity as determined accelerometery
Change in lower limb muscle power	Assessed at baseline and 12 weeks, optional repeat at 24 weeks	Change in muscle power will be determined by quadriceps strength measured using Cybex dynanometer
Change in upper limb muscle power	Assessed at baseline and 12 weeks, optional repeat at 24 weeks	Change in muscle power will be determined by handgrip strength using fysiometer
Improvement in exercise tolerance	Assessed at baseline and 12 weeks, optional repeat at 24 weeks	This will be assessed by a)change in Borg dyspnoea scale during 6MWT
Improvement in symptoms of heart failure	Assessed at baseline and 12 weeks, optional repeat at 24 weeks	This will be assessed by a change in the Minessota Living with Heart failure score
Change in frailty	Assessed at baseline and 12 weeks, optional repeat at 24 weeks	This will be assessed by a change in the Edmonton frailty questionnaire score
Exploratory outcome: Improving skeletal and cardiac energetics	Baseline and 12 weeks	31P magnetic resonance spectroscopy: Cardiac PCr/ATP
Exploratory outcome: change in fibroinflammatory biomarker panel	This will be evaluated at baseline and at 12 weeks	Exploratory analysis of the O-link fibroinflammatory biomarker panel to identify potential pathways involved in the development, progression or outcomes of HFpEF.
Change in sarcopenia	Assessed at baseline and 12 weeks, optional repeat at 24 weeks	This will be assessed by a change in the SARC-F questionnaire score

Trial Locations

Locations (3)

University of Leicester, Glenfield Hospital, Groby Road; 🇬🇧 Leicester, Leicestershire, United Kingdom

University of Manchester, Wythenshawe Hospital, Southmoor Road; 🇬🇧 Manchester, United Kingdom

University of Oxford, John Radcliffe Hospital, Headley Way; 🇬🇧 Oxford, United Kingdom