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

November 24, 2025 updated by: Tufts Medical Center
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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • 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:
        • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Appendicular Lean Mass (ALM)
Time Frame: 6 month study visit
ALM as measured by dual X-ray absorptiometry (DXA)
6 month study visit

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Protein intake
Time Frame: 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
6 month study visit
Protein intake
Time Frame: 3 month study visit
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
Time Frame: 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 month study visit
Handgrip strength
Time Frame: 3 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
3 month study visit
6-minute walk test (6MWT)
Time Frame: 6 month study visit
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)
Time Frame: 3 month study visit
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)
Time Frame: 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
6 months
Short physical performance battery (SPPB)
Time Frame: 3 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
3 months
Appendicular Lean Mass (ALM)
Time Frame: 3 month study visit
ALM as measured by dual X-ray absorptiometry (DXA)
3 month study visit

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Weight
Time Frame: 6 months
Bodyweight
6 months
Weight
Time Frame: 3 months
Bodyweight
3 months
Simplified Nutritional Appetite Questionnaire (SNAQ)
Time Frame: 6 months
Malnutrition risk assessment tool
6 months
Simplified Nutritional Appetite Questionnaire (SNAQ)
Time Frame: 3 months
Malnutrition risk assessment tool
3 months
Mini-Nutritional Assessment-Short Form (MNA-SF)
Time Frame: 6 months
Malnutrition risk assessment tool
6 months
Mini-Nutritional Assessment-Short Form (MNA-SF)
Time Frame: 3 months
Malnutrition risk assessment tool
3 months
Subjective Global Assessment (SGA)
Time Frame: 6 months
Semi-quantified assessment of cachexia per physical examination
6 months
Subjective Global Assessment (SGA)
Time Frame: 3 months
Semi-quantified assessment of cachexia per physical examination
3 months
Fat free mass (FFM)
Time Frame: 6 months
FFM as measured by dual X-ray absorptiometry (DXA)
6 months
Fat free mass (FFM)
Time Frame: 3 months
FFM as measured by dual X-ray absorptiometry (DXA)
3 months
Fat mass (FM)
Time Frame: 6 months
FM as measured by dual X-ray absorptiometry (DXA)
6 months
Fat mass (FM)
Time Frame: 3 months
FM as measured by dual X-ray absorptiometry (DXA)
3 months
Growth Differentiation Factor (GDF)-15
Time Frame: 3 months
Inflammatory and growth regulation cytokine blood concentration
3 months
Growth Differentiation Factor (GDF)-15
Time Frame: 6 months
Inflammatory and growth regulation cytokine blood concentration
6 months
Activin A and Follistatin-related gene (FSTL)-3
Time Frame: 3 months
Muscle growth regulation pathway blood concentrations
3 months
Activin A and Follistatin-related gene (FSTL)-3
Time Frame: 6 months
Muscle growth regulation pathway blood concentrations
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tufts Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 24, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 17, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 25, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 24, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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