Feasibility of Low Energy Diet in HFpEF and Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
Open, Single arm intervention, feasibility study

Detailed Description
-----------------
The aims of the proposed feasibility study are to assess whether a low-energy meal replacement plan (MRP) in patients with HFpEF and T2D: 1. Is acceptable to an older, co-morbid, multi-ethnic population The secondary objectives are to assess whether a low-energy MRP in patients with HFpEF and T2D may be: associated with improved symptoms likely to lead to favourable cardiovascular reverse remodelling likely to improve functional capacity and quality of life associated with favourable reductions in cardiovascular biomarkers associated with increased physical activity associated with favourable cardiovascular outcomes All patients will undergo the following assessments at baseline, 12-weeks and 12 months (following MRP): Anthropometry: height, weight, BMI. Haemodynamics: resting heart rate and blood pressure. 6-minute walk test +/- cardiopulmonary exercise test (if able to perform) CMR: contrast enhanced, stress perfusion CMR MLWHFQ WHODAS 2.0 (12-item version) Fasting blood test: full blood count, urea and electrolytes, HbA1c, fasting glucose, BNP, high-sensitivity troponin I, insulin and C-peptide. Plasma (≈35mL) will be stored for future biomarker analysis including metabolomics. Urinalysis for proteinuria and urine protein/creatinine ratio. Body composition; dual-energy X-ray absorptiometry (DEXA) scanning. 12. At the end of the 12-week intervention, participants will be invited to a semi-structured interview to explore qualitative aspects of the study to guide future trial design. 13. At 12 months attendance at cardiac rehabilitation will be reviewed. The MRP provided by Cambridge Weight Plan® contains  810 kcal/day (30% protein, 50% carbohydrate, 20% fat). The diet will be stopped, and a maintenance diet re-introduced once 50% excess body weight has been lost, or by 12 weeks, whichever comes first.

Official Title
-----------------
A Low-energy Meal Replacement Plan for Heart Failure With Preserved Ejection Fraction and Type 2 Diabetes: A Feasibility Study

Conditions
-----------------
Dietary Exposure

Intervention / Treatment
-----------------
* Dietary Supplement: Low energy meal replacement plan (12 weeks)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Established T2D (HbA1c ≥6.5%, duration >3months) Obesity (BMI ≥30 or ≥27 kg/m2 if black/south Asian ethnicity) Symptoms limiting exercise capacity in normal daily activities (dyspnoea or fatigue) or an established diagnosis of HF Diagnosis of HFpEF in accordance with European Society of Cardiology criteria: LV EF >50% with objective evidence of cardiac structural or functional alterations (LV hypertrophy (≥12mm); LV mass index ≥115g/m2 for males and ≥95g/m2 for females; E/e' ≥13 and a mean e' septal and lateral wall <9 cm/s; left atrial volume index >34mL/m2 or reduced global longitudinal strain (>-18%); elevated levels of natriuretic peptides (B-type natriuretic peptide >35pg/mL and/or NT-pro B-type natriuretic peptide >125pg/mL)) Exclusion Criteria: Unwilling to undertake MRP (low energy diet) HBa1c >10% Diabetes duration >12 years High-dose insulin requirement: either on full basal-bolus insulin regime or insulin requirement >1U/kg/day Have been on insulin treatment >10 years Current treatment with anti-obesity drugs Diagnosed eating disorder or purging Weight loss > 5kg in preceding 3 months (unless related to hospitalisation for HF) Absolute contraindications to MRI Severe renal impairment eGFR<30ml/min/m2 Myocardial infarction within preceding 6 months History of substance abuse Cancer undergoing active treatment Unable to consent due to lack of mental capacity Pregnancy/considering pregnancy People unable to perform activities of daily living independently or unable attend for clinical appointments without a carer/attendant Unable to read/understand English sufficiently to provide informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Low energy meal replacement plan for 12 weeks
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Low energy meal replacement plan 12 weeks | Dietary Supplement: Low energy meal replacement plan (12 weeks)<br>* Low energy meal replacement plan (12 weeks)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment and retention rates | The number of people approached, recruited and retained | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in 6 minute walk test pre- and post intervention | Meters walked within 6 minutes | 12 weeks | 
| Differences in cardiopulmonary exercise test (peak VO2) pre- and post intervention | exercise test on a static bike using minute by minute ventilatory gas analysis | 12 weeks | 
| Differences in LV remodelling (indexed LV mass) pre- and post intervention | CMR measures of cardiac geometry | 12 weeks | 
| Differences in LV function pre- and post intervention | CMR measures of cardiac function | 12 weeks | 
| Differences in E/A ratio pre- and post intervention | Standard clinical echocardiography | 12 weeks | 
| Differences in E (cm/s) pre- and post intervention | Standard clinical echocardiography | 12 weeks | 
| Differences in MV deceleration time (ms) pre- and post intervention | Standard clinical echocardiography | 12 weeks | 
| Differences in A (cm/s) pre- and post intervention | Standard clinical echocardiography | 12 weeks | 
| Differences in Septal e' pre- and post intervention | Standard clinical echocardiography | 12 weeks | 
| Differences in Lateral e' pre- and post intervention | Standard clinical echocardiography | 12 weeks | 
| Differences in Septal E/e' pre- and post intervention | Standard clinical echocardiography | 12 weeks | 
| Differences in Lateral E/e' pre- and post intervention | Standard clinical echocardiography | 12 weeks | 
| Differences in Average E/e' pre- and post intervention | Standard clinical echocardiography | 12 weeks | 
| Differences in LA volume indexed pre- and post intervention | Standard clinical echocardiography | 12 weeks | 
| Differences in TR jet velocity (m/s) pre- and post intervention | Standard clinical echocardiography | 12 weeks | 
| Differences in BMI pre- and post intervention | Weighing scales and stadiometer measurement (Kg/m2) | 12 weeks | 
| Differences in Bone Mineral Density (g/cm2) pre- and post intervention | DEXA scan | 12 weeks | 
| Differences in Total Fat mass (g) pre- and post intervention | DEXA scan | 12 weeks | 
| Differences in Total tissue fat (%) pre- and post intervention | DEXA scan | 12 weeks | 
| Differences in visceral adipose tissue mass (g) pre- and post intervention | DEXA scan | 12 weeks | 
| Differences in visceral adipose tissue volume (cm3) pre- and post intervention | DEXA scan | 12 weeks | 
| Differences in Total lean body mass (g) pre- and post intervention | DEXA scan | 12 weeks | 
| Difference in World Health Organisation Disability Schedule (WHODAS 2.0) pre- and post intervention | Scale 0 - 48 with lower scores indicating better outcome | 12 weeks | 
| Difference in Medical Research Council Dyspnoea Scale pre- and post intervention | scale 1 - 5 with lower scores indicating better outcome | 12 weeks | 
| Difference in Minnesota Living with heart Failure Questionnaire pre- and post intervention | Scale 0 - 105 with lower scores indicating better outcome | 12 weeks | 
| Differences in Fasting Glucose (mmol/L) pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in HbA1c (%) pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in HbA1c (mmol/mol) pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in B-type (ng/L) natriuretic peptide pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in hs-troponin (ng/L) natriuretic peptide pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in CRP (mg/L), natriuretic peptide pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in albumin concentration pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in albumin/creatinine ratio concentration pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in sodium (mmol/L) pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in potassium (mmol/L) pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in Urea (mmol/L) pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in creatinine (umol/L) pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in eGFR (ml/min) pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in hsTnl(ng/L) pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in hALT (iu/L) pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in ALP (iu/L)pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in LDL (mmol/L) pre- and post intervention | Biochemistry | 12 weeks | 
| Differences in kidney function pre- and post intervention | Blood analysis for eGFR (ml/min) | 12 weeks | 
| Differences in liver function pre- and post intervention | Blood analysis for ALP (iu/L) | 12 weeks | 
| Differences in the levels of physical activity pre- and post intervention | Objectively measured with an accelerometer | 12 weeks | 
| Cardiac rehabilitation uptake | The proportion of participants who were offered and attended cardiac rehabilitation following completion of the intervention (%) | 12 months | 
| The number of participants who experience any Major Adverse Cardiovascular Events (MACE) | At any point during the study if a participant experiences a major cardiovascular event this will be recorded and reported to sponsor in line with handling serious adverse events | 12 weeks |