Feasibility of Low Energy Diet in HFpEF and Type 2 Diabetes (ALLEVIATE)

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

Open, Single arm intervention, feasibility study

Study Overview

• Status: Terminated
• Conditions: Dietary Exposure
• Intervention / Treatment: Dietary supplement: Low energy meal replacement plan (12 weeks)

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:

1. associated with improved symptoms
2. likely to lead to favourable cardiovascular reverse remodelling
3. likely to improve functional capacity and quality of life
4. associated with favourable reductions in cardiovascular biomarkers
5. associated with increased physical activity
6. associated with favourable cardiovascular outcomes

All patients will undergo the following assessments at baseline, 12-weeks and 12 months (following MRP):

1. Anthropometry: height, weight, BMI.
2. Haemodynamics: resting heart rate and blood pressure.
3. 6-minute walk test +/- cardiopulmonary exercise test (if able to perform)
4. CMR: contrast enhanced, stress perfusion CMR
5. MLWHFQ
6. WHODAS 2.0 (12-item version)
7. 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.
8. Urinalysis for proteinuria and urine protein/creatinine ratio.
9. 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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Grace Walters; Phone Number: 01162044723; Email: gwmw1@leicester.ac.uk
• Study Contact Backup: Name: Emer M Brady; Phone Number: 01162044723; Email: emb29@le.acuk

Study Locations

• United Kingdom
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE3 9QP
      • Cardiovascular Research Centre (Glenfield Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Low energy meal replacement plan 12 weeks	Dietary supplement: Low energy meal replacement plan (12 weeks); Low energy meal replacement plan (12 weeks)

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

Collaborators and Investigators

• Sponsor: University of Leicester

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2020
• Primary Completion (Actual): April 21, 2023
• Study Completion (Actual): April 21, 2023

Study Registration Dates

• First Submitted: November 8, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (Actual): November 21, 2019

Study Record Updates

• Last Update Posted (Actual): April 28, 2023
• Last Update Submitted That Met QC Criteria: April 26, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 0699

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No