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

July 20, 2026 updated by: University of Leicester

A 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)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
66

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United Kingdom
      • Manchester, United Kingdom, M23 9LT
        • University of Manchester, Wythenshawe Hospital, Southmoor Road
      • Oxford, United Kingdom, OX3 9DU
        • University of Oxford, John Radcliffe Hospital, Headley Way
    • Leicestershire
      • Leicester, Leicestershire, United Kingdom, LE3 9QP
        • University of Leicester, Glenfield Hospital, Groby Road

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: 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.
Other Names:
  • Diet
Diagnostic test: Blood test
Collection of blood samples from each participant to characterise the participant's health status and fibroinflammatory markers.
Diagnostic test: Electrocardiogram
An ECG will be obtained to assess for baseline rhythm.
Other Names:
  • ECG
Diagnostic test: Accelerometery
Accelerometer (GeneActiv) measured daily activity levels continuously for 7 consecutive days.
Diagnostic test: 6 minute walk test (6MWT)
Supervised 6MWT will be performed with symptom assessment using dyspnoea scale (Borg's).
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.
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.
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.
Diagnostic test: 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, aortic distensibility 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. Additional imaging will be undertaken for 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.
Other Names:
  • CMR
Diagnostic test: Transthoracic echocardiography
Comprehensive transthoracic echocardiography, including: tissue Doppler indices of diastolic filling, exclusion of valvular abnormalities, assessment of LV size and function
Diagnostic test: Skeletal muscle strength using handgrip strength
Skeletal muscle strength will be measured using hand grip strength
Other: Assessment of quality of life and heart failure symptoms
Quality of life and HF symptoms will be assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) 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
Active Comparator: 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.
Drug: 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.
Other Names:
  • Diet
Diagnostic test: Blood test
Collection of blood samples from each participant to characterise the participant's health status and fibroinflammatory markers.
Diagnostic test: Electrocardiogram
An ECG will be obtained to assess for baseline rhythm.
Other Names:
  • ECG
Diagnostic test: Accelerometery
Accelerometer (GeneActiv) measured daily activity levels continuously for 7 consecutive days.
Diagnostic test: 6 minute walk test (6MWT)
Supervised 6MWT will be performed with symptom assessment using dyspnoea scale (Borg's).
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.
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.
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.
Diagnostic test: 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, aortic distensibility 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. Additional imaging will be undertaken for 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.
Other Names:
  • CMR
Diagnostic test: Transthoracic echocardiography
Comprehensive transthoracic echocardiography, including: tissue Doppler indices of diastolic filling, exclusion of valvular abnormalities, assessment of LV size and function
Diagnostic test: Skeletal muscle strength using handgrip strength
Skeletal muscle strength will be measured using hand grip strength
Other: Assessment of quality of life and heart failure symptoms
Quality of life and HF symptoms will be assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in the distance walked during 6 minute walk test (6MWT)
Time Frame: 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
Assessed at baseline and 12 weeks, optional repeat at 24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Beneficial reverse cardiovascular remodelling
Time Frame: Assessed at baseline and 12 weeks, optional repeat at 24 weeks
CMR-derived measures of cardiovascular remodelling defined as left ventricular mass/volume ratio
Assessed at baseline and 12 weeks, optional repeat at 24 weeks
Change in sarcopenia
Time Frame: Assessed at baseline and 12 weeks, optional repeat at 24 weeks
This will be assessed by a change in the SARC-F questionnaire score
Assessed at baseline and 12 weeks, optional repeat at 24 weeks
Exploratory outcome: Improving skeletal and cardiac energetics
Time Frame: Baseline and 12 weeks
31P magnetic resonance spectroscopy: Cardiac PCr/ATP
Baseline and 12 weeks
Change in physical activity levels
Time Frame: Assessed at baseline and 12 weeks
Improvement in physical activity will be determined by change in daily activity as determined accelerometery
Assessed at baseline and 12 weeks
Change in upper limb muscle power
Time Frame: Assessed at baseline and 12 weeks, optional repeat at 24 weeks
Change in muscle power will be determined by handgrip strength
Assessed at baseline and 12 weeks, optional repeat at 24 weeks
Improvement in exercise tolerance
Time Frame: Assessed at baseline and 12 weeks, optional repeat at 24 weeks
This will be assessed by change in Borg dyspnoea scale during 6MWT
Assessed at baseline and 12 weeks, optional repeat at 24 weeks
Improvement in symptoms of heart failure
Time Frame: Assessed at baseline and 12 weeks, optional repeat at 24 weeks
This will be assessed by a change in the Kansas City Cardiomyopathy Questionnaire score
Assessed at baseline and 12 weeks, optional repeat at 24 weeks
Exploratory outcome: change in fibroinflammatory biomarker panel
Time Frame: This will be evaluated at baseline and at 12 weeks
Exploratory analysis of the fibroinflammatory biomarker panel to identify potential pathways involved in the development, progression or outcomes of HFpEF.
This will be evaluated at baseline and at 12 weeks

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Leicester

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Leeds
University of Oxford
University of Manchester

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gerry P McCann, MD, University of Leicester

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 5, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 17, 2026

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 17, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 2, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 31, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 2, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 20, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0861

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared with other researchers.

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

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