RecruitingPhase 2Phase 3NCT05887271

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

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)


Sponsor

University of Leicester

Enrollment

63 participants

Start Date

Dec 5, 2023

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria4

  • 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

Exclusion Criteria18

  • 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
  • People currently participating in another clinical research trial that is likely to affect diet or weight change.
  • History of a severe mental illness including an eating disorder
  • \. Individuals with a diagnosis of Type 1 diabetes mellitus.

Interventions

DRUGLow 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.

DIAGNOSTIC_TESTCardiovascular 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

DIAGNOSTIC_TESTTransthoracic 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_TESTBlood test

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

DIAGNOSTIC_TESTElectrocardiogram

An ECG will be obtained to assess for baseline rhythm.

DIAGNOSTIC_TESTAccelerometery

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

DIAGNOSTIC_TEST6 minute walk test (6MWT)

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

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

Skeletal muscle strength will be measured using a cybex dynamometer.

OTHERAssessment 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

OTHERAssessment 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.

OTHERAssessment 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.

OTHERQualitative 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.


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

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NCT05887271


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