A SkeleTal Muscle Recovery Intervention With Dietary Protein in Heart Failure (ASTRID-HF)

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Muscle Atrophy
• Intervention / Treatment: Dietary supplement: Ensure Max Protein; Dietary supplement: Ensure Original

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amanda R Vest, MBBS; Phone Number: 2164446798; Email: vesta2@ccf.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Recruiting
      • Tufts Medical Center
      • Contact: Olivia Lovegreen; Phone Number: 617-636-5000; Email: OLovegreen@tuftsmedicalcenter.org
      • Principal Investigator: Indranee N Rajapreyar, MD
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Principal Investigator: Amanda R Vest, MBBS
      • Contact: Teresa Fonk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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
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
Appendicular Lean Mass (ALM)	ALM as measured by dual X-ray absorptiometry (DXA)	3 month study visit

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight	Bodyweight	6 months
Weight	Bodyweight	3 months
Simplified Nutritional Appetite Questionnaire (SNAQ)	Malnutrition risk assessment tool	6 months
Simplified Nutritional Appetite Questionnaire (SNAQ)	Malnutrition risk assessment tool	3 months
Mini-Nutritional Assessment-Short Form (MNA-SF)	Malnutrition risk assessment tool	6 months
Mini-Nutritional Assessment-Short Form (MNA-SF)	Malnutrition risk assessment tool	3 months
Subjective Global Assessment (SGA)	Semi-quantified assessment of cachexia per physical examination	6 months
Subjective Global Assessment (SGA)	Semi-quantified assessment of cachexia per physical examination	3 months
Fat free mass (FFM)	FFM as measured by dual X-ray absorptiometry (DXA)	6 months
Fat free mass (FFM)	FFM as measured by dual X-ray absorptiometry (DXA)	3 months
Fat mass (FM)	FM as measured by dual X-ray absorptiometry (DXA)	6 months
Fat mass (FM)	FM as measured by dual X-ray absorptiometry (DXA)	3 months
Growth Differentiation Factor (GDF)-15	Inflammatory and growth regulation cytokine blood concentration	3 months
Growth Differentiation Factor (GDF)-15	Inflammatory and growth regulation cytokine blood concentration	6 months
Activin A and Follistatin-related gene (FSTL)-3	Muscle growth regulation pathway blood concentrations	3 months
Activin A and Follistatin-related gene (FSTL)-3	Muscle growth regulation pathway blood concentrations	6 months

Collaborators and Investigators

• Sponsor: Tufts Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 17, 2022
• First Submitted That Met QC Criteria: November 17, 2022
• First Posted (Actual): November 25, 2022

Study Record Updates

• Last Update Posted (Estimated): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Cardiovascular Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Heart Diseases; Atrophy; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Heart Failure; Muscular Atrophy
• Other Study ID Numbers: STUDY00003095; 1R01HL167113-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data sharing plans will be reviewed by the Tufts Health Sciences IRB and no identifiable participant data will be shared outside Tufts Medical Center. A data use agreement (DUA) will be completed between the PI and collaborating sites.
• IPD Sharing Time Frame: After primary and secondary analyses have been completed and the major findings for each Aim accepted for publication.
• IPD Sharing Access Criteria: Due to the small sample size and single center location of the subjects, there remains a potential for deductive disclosure of subjects with unique clinical characteristics. Thus, the DUA will include language requiring: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No