A Randomised, Controlled Trial of a Low-energy Diet for Improving Functional Status in Heart Failure With PRESERVED Ejection Fraction Preserved Ejection Fraction
AMEND
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)
1 other identifier
interventional
63
1 country
3
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 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Dec 2023
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 2, 2023
CompletedFirst Posted
Study publicly available on registry
June 2, 2023
CompletedStudy Start
First participant enrolled
December 5, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 31, 2026
October 7, 2025
October 1, 2025
2.5 years
May 2, 2023
October 2, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in the distance walked during 6 minute walk test (6MWT)
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 Outcomes (9)
Beneficial reverse cardiovascular remodelling
Assessed at baseline and 12 weeks, optional repeat at 24 weeks
Change in physical activity levels
Assessed at baseline and 12 weeks, optional repeat at 24 weeks
Change in upper limb muscle power
Assessed at baseline and 12 weeks, optional repeat at 24 weeks
Improvement in exercise tolerance
Assessed at baseline and 12 weeks, optional repeat at 24 weeks
Improvement in symptoms of heart failure
Assessed at baseline and 12 weeks, optional repeat at 24 weeks
- +4 more secondary outcomes
Study Arms (2)
Low calorie meal replacement plan (MRP) arm
EXPERIMENTALThe 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.
Wait list control arm: Guideline driven care with attention control arm followed by optional MRP
ACTIVE COMPARATORDietary 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.
Interventions
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.
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
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
Collection of blood samples from each participant to characterise the participant's health status and fibroinflammatory markers.
An ECG will be obtained to assess for baseline rhythm.
Accelerometer (GeneActiv) measured daily activity levels continuously for 7 consecutive days.
Supervised 6MWT will be performed with symptom assessment using dyspnoea scale (Borg's).
Skeletal muscle strength will be measured using a cybex dynamometer.
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
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.
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.
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.
Eligibility Criteria
You may qualify if:
- 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
- Clinically stable for ≥ 3 months (no admissions to hospital)
- Obesity (BMI ≥30kg/m2 if white European or ≥27kg/m2 if Asian, Middle Eastern or Black ethnicity)
- Age ≥18
You may not qualify if:
- Inability to walk/undertake 6-minute walk test
- Inability to follow a low-energy MRP
- HFpEF due to infiltrative cardiomyopathy (cardiac amyloidosis or sarcoidosis), genetic hypertrophic cardiomyopathy, restrictive cardiomyopathy/pericardial disease or congenital heart disease.
- Recovered EF (previous EF \< 40%) unless reduced EF was in context of tachycardia induced cardiomyopathy (eg AF/Aflutter).
- Known heritable, idiopathic or drug-induced pulmonary arterial hypertension
- Severe chronic obstructive pulmonary disease (FEV1\< 1.0L)
- Severe primary valvular heart disease
- Anaemia (Hb\<100g/L)
- Severe renal disease (eGFR \< 30 ml/min/1.73 m2)
- Weight loss \> 5kg in preceding 3 months.
- Symptomatic gallstones (including biliary colic) or cholecystitis within last 3 months
- Active substance abuse (drugs or alcohol)
- History of bariatric surgery in the last 3 years
- Active illness likely to cause change in weight
- Women who are pregnant or are considering pregnancy
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Leicesterlead
- University of Oxfordcollaborator
- University of Manchestercollaborator
- University of Leedscollaborator
Study Sites (3)
University of Leicester, Glenfield Hospital, Groby Road
Leicester, Leicestershire, LE3 9QP, United Kingdom
University of Manchester, Wythenshawe Hospital, Southmoor Road
Manchester, M23 9LT, United Kingdom
University of Oxford, John Radcliffe Hospital, Headley Way
Oxford, OX3 9DU, United Kingdom
Related Publications (1)
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.
PMID: 39880434DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Gerry P McCann, MD
University of Leicester
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- Participants and investigator will not be blinded to treatment allocation (open label) however, the team analysing the outcomes will be blinded to treatment allocation.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 2, 2023
First Posted
June 2, 2023
Study Start
December 5, 2023
Primary Completion (Estimated)
May 31, 2026
Study Completion (Estimated)
May 31, 2026
Last Updated
October 7, 2025
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will not share
Individual participant data will not be shared with other researchers.