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

NCT ID: NCT05887271

Last Updated: 2025-10-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

63 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-05

Study Completion Date

2026-05-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multi-centre, prospective, open-label blinded end-point randomized wait-list controlled trial of low-energy Meal Replacement Plan (MRP) versus guideline-driven care with attention control, and a nested qualitative sub-study.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Participants and investigator will not be blinded to treatment allocation (open label) however, the team analysing the outcomes will be blinded to treatment allocation.

Study Groups

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Low calorie meal replacement plan (MRP) arm

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.

Group Type EXPERIMENTAL

Low calorie meal replacement plan

Intervention Type DRUG

Meal replacement diet containing \~850 kcal/day (40% protein, 50% carbohydrate, 10% fat) supplied by Counterweight® (www.counterweight.org).The meal replacement plan will comprise of 3-4 meal packs/day (to equate to 850 kcal) with sweet and savoury options, and an allowance of 100ml semi-skimmed milk or a non-dairy alternative.

Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy

Intervention Type DIAGNOSTIC_TEST

CMR scanning performed on a 3T MRI scanner. Standardised protocol incorporating cine functional assessment to determine LV mass, systolic function and left atrial volumes; global systolic strain and diastolic strain rates will be assessed by tagging and with tissue tracking analysis from cine images, adenosine rest and stress myocardial perfusion to assess reserve index and qualitative perfusion defects as previously described, aortic distensibility and pulse wave velocity to measure aortic stiffness, delayed contrast enhancement for assessment of LV fibrosis and evidence of previous myocardial infarction. Myocardial and liver triglyceride content will be assessed using the modified Hepafat® sequence or 1H MR spectroscopy at the inter ventricular septum. DIXON technique for the quantification of visceral adiposity and subcutaneous adipose tissue. Cardiac 31P magnetic resonance spectroscopy imaging to assess cardiac muscle energetics according to a standardised operating procedure

Transthoracic echocardiography

Intervention Type DIAGNOSTIC_TEST

Comprehensive transthoracic echocardiography, including: tissue Doppler indices of diastolic filling and speckle tracking for systolic and diastolic strain/strain rate, exclusion of valvular abnormalities, assessment of LV size and function

Blood test

Intervention Type DIAGNOSTIC_TEST

Collection of blood samples from each participant to characterise the participant's health status and fibroinflammatory markers.

Electrocardiogram

Intervention Type DIAGNOSTIC_TEST

An ECG will be obtained to assess for baseline rhythm.

Accelerometery

Intervention Type DIAGNOSTIC_TEST

Accelerometer (GeneActiv) measured daily activity levels continuously for 7 consecutive days.

6 minute walk test (6MWT)

Intervention Type DIAGNOSTIC_TEST

Supervised 6MWT will be performed with symptom assessment using dyspnoea scale (Borg's).

Skeletal muscle strength using handgrip strength and quadriceps (Cybex dynamometer)

Intervention Type DIAGNOSTIC_TEST

Skeletal muscle strength will be measured using a cybex dynamometer.

Assessment of quality of life and heart failure symptoms

Intervention Type OTHER

Quality of life and HF symptoms will be assessed using the Minnesota Living with Heart Failure (MLWHF) questionnaire, which is used as a standardised measure of self-reported health status, and HF symptoms and is considered to have a good discriminatory power and validity

Assessment of sarcopenia

Intervention Type OTHER

Participants will be assessed for presence of sarcopenia using the Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls (SARC-F) questionnaire. It is a robust tool for diagnosis of sarcopenia and prediction poor physical function, with excellent specificity in multimorbid individuals.

Assessment of frailty

Intervention Type OTHER

Frailty will be assessed using the Edmonton Frail Scale (EFS). The EFS is a multidimensional frailty assessment which assesses multiple domains of frailty including functional independence, social support, cognition, medication use, and mood.

Qualitative interview

Intervention Type OTHER

Participants in the MRP and control groups will be invited to attend a focused semi-structured, 1-2-1 interview aimed to elicit barriers and enablers to the MRP and describe their perspective on the relationship between healthy eating and health interview during the 12-week visit. Participants who complete or drop out will be eligible. Inclusion of participants in the control arm will allow us to compare the experiences of MRP versus health coaching and detect any specific issues people face when trying to introduce lifestyle changes themselves.

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

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.

Group Type ACTIVE_COMPARATOR

Low calorie meal replacement plan

Intervention Type DRUG

Meal replacement diet containing \~850 kcal/day (40% protein, 50% carbohydrate, 10% fat) supplied by Counterweight® (www.counterweight.org).The meal replacement plan will comprise of 3-4 meal packs/day (to equate to 850 kcal) with sweet and savoury options, and an allowance of 100ml semi-skimmed milk or a non-dairy alternative.

Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy

Intervention Type DIAGNOSTIC_TEST

CMR scanning performed on a 3T MRI scanner. Standardised protocol incorporating cine functional assessment to determine LV mass, systolic function and left atrial volumes; global systolic strain and diastolic strain rates will be assessed by tagging and with tissue tracking analysis from cine images, adenosine rest and stress myocardial perfusion to assess reserve index and qualitative perfusion defects as previously described, aortic distensibility and pulse wave velocity to measure aortic stiffness, delayed contrast enhancement for assessment of LV fibrosis and evidence of previous myocardial infarction. Myocardial and liver triglyceride content will be assessed using the modified Hepafat® sequence or 1H MR spectroscopy at the inter ventricular septum. DIXON technique for the quantification of visceral adiposity and subcutaneous adipose tissue. Cardiac 31P magnetic resonance spectroscopy imaging to assess cardiac muscle energetics according to a standardised operating procedure

Transthoracic echocardiography

Intervention Type DIAGNOSTIC_TEST

Comprehensive transthoracic echocardiography, including: tissue Doppler indices of diastolic filling and speckle tracking for systolic and diastolic strain/strain rate, exclusion of valvular abnormalities, assessment of LV size and function

Blood test

Intervention Type DIAGNOSTIC_TEST

Collection of blood samples from each participant to characterise the participant's health status and fibroinflammatory markers.

Electrocardiogram

Intervention Type DIAGNOSTIC_TEST

An ECG will be obtained to assess for baseline rhythm.

Accelerometery

Intervention Type DIAGNOSTIC_TEST

Accelerometer (GeneActiv) measured daily activity levels continuously for 7 consecutive days.

6 minute walk test (6MWT)

Intervention Type DIAGNOSTIC_TEST

Supervised 6MWT will be performed with symptom assessment using dyspnoea scale (Borg's).

Skeletal muscle strength using handgrip strength and quadriceps (Cybex dynamometer)

Intervention Type DIAGNOSTIC_TEST

Skeletal muscle strength will be measured using a cybex dynamometer.

Assessment of quality of life and heart failure symptoms

Intervention Type OTHER

Quality of life and HF symptoms will be assessed using the Minnesota Living with Heart Failure (MLWHF) questionnaire, which is used as a standardised measure of self-reported health status, and HF symptoms and is considered to have a good discriminatory power and validity

Assessment of sarcopenia

Intervention Type OTHER

Participants will be assessed for presence of sarcopenia using the Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls (SARC-F) questionnaire. It is a robust tool for diagnosis of sarcopenia and prediction poor physical function, with excellent specificity in multimorbid individuals.

Assessment of frailty

Intervention Type OTHER

Frailty will be assessed using the Edmonton Frail Scale (EFS). The EFS is a multidimensional frailty assessment which assesses multiple domains of frailty including functional independence, social support, cognition, medication use, and mood.

Qualitative interview

Intervention Type OTHER

Participants in the MRP and control groups will be invited to attend a focused semi-structured, 1-2-1 interview aimed to elicit barriers and enablers to the MRP and describe their perspective on the relationship between healthy eating and health interview during the 12-week visit. Participants who complete or drop out will be eligible. Inclusion of participants in the control arm will allow us to compare the experiences of MRP versus health coaching and detect any specific issues people face when trying to introduce lifestyle changes themselves.

Interventions

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Low calorie meal replacement plan

Meal replacement diet containing \~850 kcal/day (40% protein, 50% carbohydrate, 10% fat) supplied by Counterweight® (www.counterweight.org).The meal replacement plan will comprise of 3-4 meal packs/day (to equate to 850 kcal) with sweet and savoury options, and an allowance of 100ml semi-skimmed milk or a non-dairy alternative.

Intervention Type DRUG

Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy

CMR scanning performed on a 3T MRI scanner. Standardised protocol incorporating cine functional assessment to determine LV mass, systolic function and left atrial volumes; global systolic strain and diastolic strain rates will be assessed by tagging and with tissue tracking analysis from cine images, adenosine rest and stress myocardial perfusion to assess reserve index and qualitative perfusion defects as previously described, aortic distensibility and pulse wave velocity to measure aortic stiffness, delayed contrast enhancement for assessment of LV fibrosis and evidence of previous myocardial infarction. Myocardial and liver triglyceride content will be assessed using the modified Hepafat® sequence or 1H MR spectroscopy at the inter ventricular septum. DIXON technique for the quantification of visceral adiposity and subcutaneous adipose tissue. Cardiac 31P magnetic resonance spectroscopy imaging to assess cardiac muscle energetics according to a standardised operating procedure

Intervention Type DIAGNOSTIC_TEST

Transthoracic echocardiography

Comprehensive transthoracic echocardiography, including: tissue Doppler indices of diastolic filling and speckle tracking for systolic and diastolic strain/strain rate, exclusion of valvular abnormalities, assessment of LV size and function

Intervention Type DIAGNOSTIC_TEST

Blood test

Collection of blood samples from each participant to characterise the participant's health status and fibroinflammatory markers.

Intervention Type DIAGNOSTIC_TEST

Electrocardiogram

An ECG will be obtained to assess for baseline rhythm.

Intervention Type DIAGNOSTIC_TEST

Accelerometery

Accelerometer (GeneActiv) measured daily activity levels continuously for 7 consecutive days.

Intervention Type DIAGNOSTIC_TEST

6 minute walk test (6MWT)

Supervised 6MWT will be performed with symptom assessment using dyspnoea scale (Borg's).

Intervention Type DIAGNOSTIC_TEST

Skeletal muscle strength using handgrip strength and quadriceps (Cybex dynamometer)

Skeletal muscle strength will be measured using a cybex dynamometer.

Intervention Type DIAGNOSTIC_TEST

Assessment of quality of life and heart failure symptoms

Quality of life and HF symptoms will be assessed using the Minnesota Living with Heart Failure (MLWHF) questionnaire, which is used as a standardised measure of self-reported health status, and HF symptoms and is considered to have a good discriminatory power and validity

Intervention Type OTHER

Assessment of sarcopenia

Participants will be assessed for presence of sarcopenia using the Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls (SARC-F) questionnaire. It is a robust tool for diagnosis of sarcopenia and prediction poor physical function, with excellent specificity in multimorbid individuals.

Intervention Type OTHER

Assessment of frailty

Frailty will be assessed using the Edmonton Frail Scale (EFS). The EFS is a multidimensional frailty assessment which assesses multiple domains of frailty including functional independence, social support, cognition, medication use, and mood.

Intervention Type OTHER

Qualitative interview

Participants in the MRP and control groups will be invited to attend a focused semi-structured, 1-2-1 interview aimed to elicit barriers and enablers to the MRP and describe their perspective on the relationship between healthy eating and health interview during the 12-week visit. Participants who complete or drop out will be eligible. Inclusion of participants in the control arm will allow us to compare the experiences of MRP versus health coaching and detect any specific issues people face when trying to introduce lifestyle changes themselves.

Intervention Type OTHER

Other Intervention Names

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Diet CMR ECG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Oxford

OTHER

Sponsor Role collaborator

University of Manchester

OTHER

Sponsor Role collaborator

University of Leeds

OTHER

Sponsor Role collaborator

University of Leicester

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gerry P McCann, MD

Role: PRINCIPAL_INVESTIGATOR

University of Leicester

Locations

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University of Leicester, Glenfield Hospital, Groby Road

Leicester, Leicestershire, United Kingdom

Site Status RECRUITING

University of Manchester, Wythenshawe Hospital, Southmoor Road

Manchester, , United Kingdom

Site Status RECRUITING

University of Oxford, John Radcliffe Hospital, Headley Way

Oxford, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Sarah L Ayton, MBBS

Role: CONTACT

+44 (0)116 258 3038

Emer M Brady, PhD

Role: CONTACT

44 (0)116 204 4723

Facility Contacts

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Joanna M Bilak

Role: primary

07949539001

Emer M Brady

Role: backup

Christopher Miller

Role: primary

Oliver Rider

Role: primary

References

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Bilak JM, Squire I, Wormleighton JV, Brown RL, Hadjiconstantinou M, Robertson N, Davies MJ, Yates T, Asad M, Levelt E, Pan J, Rider O, Soltani F, Miller C, Gulsin GS, Brady EM, McCann GP. The Protocol for the Multi-Ethnic, multi-centre raNdomised controlled trial of a low-energy Diet for improving functional status in heart failure with Preserved ejection fraction (AMEND Preserved). BMJ Open. 2025 Jan 28;15(1):e094722. doi: 10.1136/bmjopen-2024-094722.

Reference Type DERIVED
PMID: 39880434 (View on PubMed)

Other Identifiers

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0861

Identifier Type: -

Identifier Source: org_study_id

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