Clinical trial NCT05887271: A Randomised, Controlled Trial of a Low-energy Diet for Improving Functional Status in Heart Failure With PRESERVED Ejection Fraction Preserved Ejection Fraction
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Heart Failure With Preserved Ejection Fraction
Heart Failure, Diastolic
Diabetes Mellitus, Type 2
Diabetes Mellitus Type 2 in Obese
Obesity Adult Onset
Keywords: Heart failure with preserved ejection fraction
Diastolic heart failure
Type 2 diabetes mellitus
Obesity
Meal replacement plan
Cardiac magnetic resonance imaging
Exercise intolerance
Diabetes remission
Lead sponsor: University of Leicester
Sponsor class: OTHER
Collaborators: name: University of Oxford
name: University of Manchester
First posted: 2023-06-02
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-centre, prospective, open-label blinded end-point randomized controlled trial of low-energy Meal Replacement Plan (MRP) versus guideline-driven care with attention control, and a nested qualitative sub-study.
Primary purpose: TREATMENT

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 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in the distance walked during 6 minute walk test (6MWT)
timeFrame: Assessed at baseline and 12 weeks, optional repeat at 24 weeks
Secondary outcomes:
measure: Beneficial reverse cardiovascular remodelling
timeFrame: Assessed at baseline and 12 weeks, optional repeat at 24 weeks
measure: Change in physical activity levels
timeFrame: Assessed at baseline and 12 weeks, optional repeat at 24 weeks
measure: Change in lower limb muscle power
timeFrame: Assessed at baseline and 12 weeks, optional repeat at 24 weeks
measure: Change in upper limb muscle power
timeFrame: Assessed at baseline and 12 weeks, optional repeat at 24 weeks
measure: Improvement in exercise tolerance
timeFrame: Assessed at baseline and 12 weeks, optional repeat at 24 weeks
measure: Improvement in symptoms of heart failure
timeFrame: Assessed at baseline and 12 weeks, optional repeat at 24 weeks
measure: Change in frailty
timeFrame: Assessed at baseline and 12 weeks, optional repeat at 24 weeks
measure: Change in sarcopenia
timeFrame: Assessed at baseline and 12 weeks, optional repeat at 24 weeks
measure: Exploratory outcome: Improving skeletal and cardiac energetics
timeFrame: Baseline and 12 weeks
measure: Exploratory outcome: change in fibroinflammatory biomarker panel
timeFrame: This will be evaluated at baseline and at 12 weeks
Other outcomes:
Locations:
city: Leicester
country: United Kingdom
facility: University of Leicester, Glenfield Hospital, Groby Road
state: Leicestershire
city: Manchester
country: United Kingdom
facility: University of Manchester, Wythenshawe Hospital, Southmoor Road
city: Oxford
country: United Kingdom
facility: University of Oxford, John Radcliffe Hospital, Headley Way
Study officials:
affiliation: University of Leicester
name: Gerry P McCann, MD
role: PRINCIPAL_INVESTIGATOR
References: