Heart Failure, Muscle Atrophy
Conditions
Brief summary
Severe skeletal wasting and catabolic weight loss are highly common among patients with heart failure with reduced ejection fraction (HFrEF). This prospective randomized controlled trial will compare changes in the muscle mass in the arms and the legs (appendicular lean mass) in patients with HFrEF randomized between 3 groups of no, low- or high-dose protein supplementation. The dietary protein supplementation will be Ensure(R) products manufactured by Abbott Nutrition. The Investigators hypothesize that skeletal muscle wasting in HFrEF is promoted by neurohumoral activation of catabolic metabolism (such as GDF-15 and ActRII pathways) and can be at least partially reversed by increased dietary protein intake. It is anticipated that this study will determine whether dietary protein supplementation helps to prevent muscle wasting and will advance understanding of the GDF-15 and ActRII muscle wasting pathways.
Interventions
DIETARY_SUPPLEMENTEnsure Max Protein
Ensure Max Protein, 1 bottle daily (330 mL), 30 grams protein
DIETARY_SUPPLEMENTEnsure Original
Ensure Original, 1 bottle daily (237 mL), 9 grams protein
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Tufts Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Left ventricular ejection fraction (LVEF) ≤40%, New York Heart Association (NHYA) class II to IV symptoms or N-terminal pro B-natriuretic peptide (NT-proBNP) \>300 pg/mL 2. Age 18 years to 100 years, inclusive 3. Receiving guideline-directed medical therapy (GDMT), unless contraindicated or not tolerated 4. Any of the following markers of severe HF within prior 12 months: i) Inotropic therapy; ii) 1 or more HF hospitalizations; iii) LVEF ≤25%; iv) Peak oxygen consumption (VO2) \<50% predicted or ≤16 mL/kg/min; v) 6-minute walk distance \<300 meters; vi) Unintentional weight loss \>5% of bodyweight over the past year; vii) Moderate or severe muscle wasting on physical examination; viii) NT-proBNP ≥900 pg/mL
Exclusion criteria
1. Pregnancy, planning to become pregnant, or women of reproductive potential unwilling to complete pre-DXA urine pregnancy test before first DXA or randomization 2. History of left ventricular assist device (LVAD), heart transplantation, or estimated glomerular filtration rate (eGFR) \<20 mL/min/1.73 m2 3. An identified clinical disorder associated with skeletal muscle weakness/wasting (e.g., muscular dystrophy, mitochondrial disorder, active cancer, modified Rankin score greater or equal to 4 post-stroke) 4. Milk allergy, protein allergy, lactose intolerance, and galactosemia 5. Weight ≥350 pounds and/or BMI ≥40 kg/m2 6. Initiation of obesity-dosed GLP-1 or GIP/GLP-1 agonist within 3 months prior to screening, or clinical intention to begin such an anti-obesity medication within the next 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Appendicular Lean Mass (ALM) | 6 month study visit | ALM as measured by dual X-ray absorptiometry (DXA) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Appendicular Lean Mass (ALM) | 3 month study visit | ALM as measured by dual X-ray absorptiometry (DXA) |
| Protein intake | 6 month study visit | Dietary protein intake in g/kg/day, averaged over 3 days, which is calculated by entering recorded dietary intake from facilitate food record into the Food Processor® software |
| Handgrip strength | 6 month study visit | Strength in dominant hand assessed with 3 attempts using a hydraulic hand dynamometer in the dominant hand (Baseline® Evaluation Instruments Fabrication Enterprises Inc., Irvington NY) and the mean calculated |
| 6-minute walk test (6MWT) | 6 month study visit | 6-minute walk test measured over 100-foot laps, with 0 feet assigned if no independent ambulation is possible |
| Short physical performance battery (SPPB) | 6 months | SPPB assesses balance, gait, strength, and endurance, by recording the ability to stand for up to 10 seconds with feet in the side-by-side, semi-tandem, and tandem positions; time to complete a 4-meter walk; and time to rise from a chair and return to the seated position 5 times |
Other
| Measure | Time frame | Description |
|---|---|---|
| Growth Differentiation Factor (GDF)-15 | 3 months | Inflammatory and growth regulation cytokine blood concentration |
| Fat free mass (FFM) | 6 months | FFM as measured by dual X-ray absorptiometry (DXA) |
| Activin A and Follistatin-related gene (FSTL)-3 | 3 months | Muscle growth regulation pathway blood concentrations |
| Fat mass (FM) | 6 months | FM as measured by dual X-ray absorptiometry (DXA) |
| Weight | 6 months | Bodyweight |
| Simplified Nutritional Appetite Questionnaire (SNAQ) | 6 months | Malnutrition risk assessment tool |
| Mini-Nutritional Assessment-Short Form (MNA-SF) | 6 months | Malnutrition risk assessment tool |
| Subjective Global Assessment (SGA) | 6 months | Semi-quantified assessment of cachexia per physical examination |
Countries
United States
Contacts
Primary ContactAmanda R Vest, MBBS
Outcome results
None listed