A SkeleTal Muscle Recovery Intervention With Dietary Protein in Heart Failure

Study Overview
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Brief Summary
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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.

Official Title
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A SkeleTal Muscle Recovery Intervention With Dietary Protein in Heart Failure

Conditions
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Heart Failure, Muscle Atrophy

Intervention / Treatment
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* Dietary Supplement: Ensure Max Protein
* Dietary Supplement: Ensure Original


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Age 18 years to 100 years, inclusive Receiving guideline-directed medical therapy (GDMT), unless contraindicated or not tolerated 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 Exclusion Criteria: Pregnancy, planning to become pregnant, or women of reproductive potential unwilling to complete pre-DXA urine pregnancy test before first DXA or randomization History of left ventricular assist device (LVAD), heart transplantation, or estimated glomerular filtration rate (eGFR) <20 mL/min/1.73 m2 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) Milk allergy, protein allergy, lactose intolerance, and galactosemia Weight ≥350 pounds and/or BMI ≥40 kg/m2

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental arm<br>30 g/day protein supplementation (1 Ensure Max Protein® bottle) | Dietary Supplement: Ensure Max Protein<br>* Ensure Max Protein, 1 bottle daily (330 mL), 30 grams protein<br>|
| Active Comparator: Sham comparator arm<br>9 g/day protein supplementation (1 Ensure Original® bottle) | Dietary Supplement: Ensure Original<br>* Ensure Original, 1 bottle daily (237 mL), 9 grams protein<br>|
| No Intervention: No intervention arm<br>0 g/day protein supplementation (no Ensure bottles) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Appendicular Lean Mass (ALM) | ALM as measured by dual X-ray absorptiometry (DXA) | 6 month study visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Appendicular Lean Mass (ALM) | ALM as measured by dual X-ray absorptiometry (DXA) | 3 month study visit | 
| Protein intake | 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 | 6 month study visit | 
| Protein intake | Dietary protein intake in g/kg/day, averaged over 3 days, which is calculated by entering recorded dietary intake from facilitated food record into the Food Processor® software | 3 month study visit | 
| Handgrip strength | 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 month study visit | 
| Handgrip strength | 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 | 3 month study visit | 
| 6-minute walk test (6MWT) | 6-minute walk test measured over 100-foot laps, with 0 feet assigned if no independent ambulation is possible | 6 month study visit | 
| 6-minute walk test (6MWT) | 6-minute walk test measured over 100-foot laps, with 0 feet assigned if no independent ambulation is possible | 3 month study visit | 
| Short physical performance battery (SPPB) | 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 | 6 months | 
| Short physical performance battery (SPPB) | 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 | 3 months |