Clinical trial NCT04173117: Feasibility of Low Energy Diet in HFpEF and Type 2 Diabetes
Official title: A Low-energy Meal Replacement Plan for Heart Failure With Preserved Ejection Fraction and Type 2 Diabetes: A Feasibility Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Dietary Exposure
Lead sponsor: University of Leicester
Sponsor class: OTHER
First posted: 2019-11-21
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Low energy meal replacement plan for 12 weeks
Primary purpose: TREATMENT

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:

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.

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

Primary outcomes:
measure: Recruitment and retention rates
timeFrame: 16 weeks
Secondary outcomes:
measure: Differences in 6 minute walk test pre- and post intervention
timeFrame: 12 weeks
measure: Differences in cardiopulmonary exercise test (peak VO2) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in LV remodelling (indexed LV mass) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in LV function pre- and post intervention
timeFrame: 12 weeks
measure: Differences in E/A ratio pre- and post intervention
timeFrame: 12 weeks
measure: Differences in E (cm/s) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in MV deceleration time (ms) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in A (cm/s) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in Septal e' pre- and post intervention
timeFrame: 12 weeks
measure: Differences in Lateral e' pre- and post intervention
timeFrame: 12 weeks
measure: Differences in Septal E/e' pre- and post intervention
timeFrame: 12 weeks
measure: Differences in Lateral E/e' pre- and post intervention
timeFrame: 12 weeks
measure: Differences in Average E/e' pre- and post intervention
timeFrame: 12 weeks
measure: Differences in LA volume indexed pre- and post intervention
timeFrame: 12 weeks
measure: Differences in TR jet velocity (m/s) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in BMI pre- and post intervention
timeFrame: 12 weeks
measure: Differences in Bone Mineral Density (g/cm2) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in Total Fat mass (g) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in Total tissue fat (%) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in visceral adipose tissue mass (g) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in visceral adipose tissue volume (cm3) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in Total lean body mass (g) pre- and post intervention
timeFrame: 12 weeks
measure: Difference in World Health Organisation Disability Schedule (WHODAS 2.0) pre- and post intervention
timeFrame: 12 weeks
measure: Difference in Medical Research Council Dyspnoea Scale pre- and post intervention
timeFrame: 12 weeks
measure: Difference in Minnesota Living with heart Failure Questionnaire pre- and post intervention
timeFrame: 12 weeks
measure: Differences in Fasting Glucose (mmol/L) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in HbA1c (%) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in HbA1c (mmol/mol) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in B-type (ng/L) natriuretic peptide pre- and post intervention
timeFrame: 12 weeks
measure: Differences in hs-troponin (ng/L) natriuretic peptide pre- and post intervention
timeFrame: 12 weeks
measure: Differences in CRP (mg/L), natriuretic peptide pre- and post intervention
timeFrame: 12 weeks
measure: Differences in albumin concentration pre- and post intervention
timeFrame: 12 weeks
measure: Differences in albumin/creatinine ratio concentration pre- and post intervention
timeFrame: 12 weeks
measure: Differences in sodium (mmol/L) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in potassium (mmol/L) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in Urea (mmol/L) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in creatinine (umol/L) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in eGFR (ml/min) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in hsTnl(ng/L) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in hALT (iu/L) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in ALP (iu/L)pre- and post intervention
timeFrame: 12 weeks
measure: Differences in LDL (mmol/L) pre- and post intervention
timeFrame: 12 weeks
measure: Differences in kidney function pre- and post intervention
timeFrame: 12 weeks
measure: Differences in liver function pre- and post intervention
timeFrame: 12 weeks
measure: Differences in the levels of physical activity pre- and post intervention
timeFrame: 12 weeks
measure: Cardiac rehabilitation uptake
timeFrame: 12 months
measure: The number of participants who experience any Major Adverse Cardiovascular Events (MACE)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Leicester
country: United Kingdom
facility: Cardiovascular Research Centre (Glenfield Hospital)
state: Leicestershire
Study officials:
References: