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

May 31, 2023 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 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

102

Phase

  • 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 Backup

Study Locations

  • United Kingdom
      • Manchester, United Kingdom, M23 9LT
        • Recruiting
        • University of Manchester, Wythenshawe Hospital, Southmoor Road
        • Contact:
        • Principal Investigator:
          • Christopher Miller
      • Oxford, United Kingdom, OX3 9DU
        • Recruiting
        • University of Oxford, John Radcliffe Hospital, Headley Way
        • Contact:
        • Principal Investigator:
          • Oliver Rider
    • Leicestershire
      • Leicester, Leicestershire, United Kingdom, LE3 9QP
        • Recruiting
        • University of Leicester, Glenfield Hospital, Groby Road
        • Contact:
        • Contact:
        • Principal Investigator:
          • Gerry P McCann

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

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 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

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
Intervention / Treatment
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.
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: 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
Other Names:
  • CMR
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
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).
Diagnostic test: Skeletal muscle strength using handgrip strength and quadriceps (Cybex dynamometer)
Skeletal muscle strength will be measured using a cybex dynamometer.
Other: 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
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: Skeletal muscle magnetic resonance spectroscopy
Assessment of skeletal muscle volume (quadriceps and calf muscle) using MRI, and 31P-magnetic resonance spectroscopy (31P-MRS) of the skeletal muscle using fysiometer and during isometric exercise at rest and after 5 minutes of exercise to assess changes in muscle energetics at rest and on exercise.
Active Comparator: Guideline driven care with attention control arm
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.
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 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
Other Names:
  • CMR
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
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).
Diagnostic test: Skeletal muscle strength using handgrip strength and quadriceps (Cybex dynamometer)
Skeletal muscle strength will be measured using a cybex dynamometer.
Other: 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
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: Skeletal muscle magnetic resonance spectroscopy
Assessment of skeletal muscle volume (quadriceps and calf muscle) using MRI, and 31P-magnetic resonance spectroscopy (31P-MRS) of the skeletal muscle using fysiometer and during isometric exercise at rest and after 5 minutes of exercise to assess changes in muscle energetics at rest and on exercise.

What is the study measuring?

Primary Outcome Measures

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

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 physical activity levels
Time Frame: 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
Assessed at baseline and 12 weeks, optional repeat at 24 weeks
Change in lower limb muscle power
Time Frame: 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
Assessed at baseline and 12 weeks, optional repeat at 24 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 using fysiometer
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 a)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 Minessota Living with Heart failure score
Assessed at baseline and 12 weeks, optional repeat at 24 weeks
Change in frailty
Time Frame: Assessed at baseline and 12 weeks, optional repeat at 24 weeks
This will be assessed by a change in the Edmonton frailty questionnaire score
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
Exploratory outcome: change in fibroinflammatory biomarker panel
Time Frame: 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.
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

University of Leicester

Collaborators

University of Oxford
University of Manchester

Investigators

  • Principal Investigator: Gerry P McCann, MD, University of Leicester

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)

March 29, 2023

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

May 2, 2023

First Submitted That Met QC Criteria

May 31, 2023

First Posted (Estimated)

June 2, 2023

Study Record Updates

Last Update Posted (Estimated)

June 2, 2023

Last Update Submitted That Met QC Criteria

May 31, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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