High-Protein Nutrition for Heart Failure-related Muscle Wasting

(ASTRID-HF Trial)

Recruiting at 1 trial location

Overseen By Amanda R Vest, MBBS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Tufts Medical Center

Disqualifiers: Pregnancy, LVAD, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 6 months

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether high-protein nutrition can prevent muscle wasting in people with heart failure, specifically those with reduced ejection fraction. Participants will be divided into three groups: one with no protein supplement, one with a low dose, and one with a high dose of Ensure Max Protein products. The goal is to determine if increased protein intake improves muscle mass in the arms and legs. The trial seeks individuals with heart failure who have experienced frequent hospitalizations or significant weight loss in the past year. As an unphased trial, it offers a unique opportunity to contribute to understanding the potential benefits of high-protein nutrition for heart failure patients.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be on guideline-directed medical therapy unless it's contraindicated or not tolerated.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that high-protein diets, such as those including Ensure Max Protein, are generally safe for people with heart failure. Studies indicate that increasing protein intake to about 1.5 grams per kilogram of body weight daily does not harm the kidneys in these patients. As a result, high-protein supplements are well-tolerated and may help prevent muscle loss.

Ensure Max Protein is designed to help build muscle, which is crucial for people with heart failure who often experience muscle loss. There have been no major reports of negative effects from using this type of protein supplement in people with heart failure, making it a promising option for those wanting to maintain muscle mass. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because they focus on nutritional supplementation to address muscle wasting in heart failure patients, an area not typically emphasized by standard medications like ACE inhibitors or beta-blockers. Ensure Max Protein and Ensure Original differ in their protein content, providing 30 grams and 9 grams of protein per day, respectively, which could directly support muscle maintenance and growth. This approach is novel as it targets muscle wasting through dietary intervention rather than pharmacological means, offering a potentially safer and more accessible option for improving patient outcomes.

What evidence suggests that this trial's treatments could be effective for heart failure-related muscle wasting?

Research has shown that high-protein diets can help people with heart failure improve muscle mass and strength. In this trial, participants in the experimental arm will receive Ensure Max Protein, which studies have found boosts muscle protein, crucial for those who often lose muscle. This supplement may lead to small but meaningful improvements in muscle function. Participants in the sham comparator arm will receive Ensure Original, which offers lower protein supplementation. The protein in Ensure Max Protein could help prevent muscle loss by supporting muscle rebuilding. Overall, protein supplements may offer a promising way to address muscle loss in heart failure patients. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-100 with heart failure and reduced ejection fraction (HFrEF), experiencing muscle wasting. They must be on standard heart failure treatments, have a left ventricular ejection fraction ≤40%, and show signs of severe heart failure like hospitalizations or significant weight loss. Excluded are pregnant women, those with certain muscle disorders, severe kidney issues, allergies to milk/protein/lactose intolerance/galactosemia, or very high body weight/BMI.

Inclusion Criteria

I am on standard treatment for my condition, unless I can't tolerate it.

I have had severe heart failure signs in the last year, like hospital stays or major weight loss.

My heart's pumping ability is reduced, and I have moderate to severe heart symptoms or high NT-proBNP levels.

Exclusion Criteria

You are allergic to milk or have trouble digesting milk sugar.

I weigh at least 350 pounds or my BMI is 40 or more.

I have a condition that causes muscle weakness or wasting.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dietary protein supplementation with Ensure products, randomized between no, low, or high-dose groups

6 months

Monthly visits for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ensure Max Protein
• Ensure Original

Trial Overview The study tests if different doses of dietary protein from Ensure(R) products can prevent muscle wasting in patients with HFrEF. Participants will be divided into three groups: one without protein supplementation, one with a low dose, and another with a high dose. The goal is to see if increased dietary protein affects muscle mass in the limbs.

How Is the Trial Designed?

Group I: Experimental arm Experimental Treatment 1 Intervention

30 g/day protein supplementation (1 Ensure Max Protein® bottle)

Group II: No intervention arm Active Control 1 Intervention

0 g/day protein supplementation (no Ensure bottles)

Group III: Sham comparator arm Active Control 1 Intervention

9 g/day protein supplementation (1 Ensure Original® bottle)

Ensure Max Protein is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ensure for:

• Nutritional supplement for patients with malnutrition, including those with heart failure

Approved in European Union as Ensure for:

• Nutritional supplement for patients with malnutrition, including those with heart failure

Approved in Canada as Ensure for:

• Nutritional supplement for patients with malnutrition, including those with heart failure

Who Is Running the Clinical Trial?

Tufts Medical Center

Lead Sponsor

Trials

264

Recruited

264,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study of 178 pre-frail older adults over 3 months, those who received leucine-enriched protein supplementation combined with exercise showed significant improvements in physical function, including gait speed and muscle strength, compared to those who only received nutrition support.

Both the nutrition with exercise and nutrition-only groups experienced reductions in inflammatory biomarkers IL-6 and TNF-α, indicating potential health benefits, although these improvements were not maintained after 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of exercise and leucine-enriched protein supplementation on physical function, body composition, and inflammation in pre-frail older adults: a quasi-experimental study. Merchant, RA., Chan, YH., Anbarasan, D., et al.[2023]

Sarcopenia and muscle wasting are expected to increase in older adults due to COVID-19 hospitalizations and lockdowns, driven by factors like physical inactivity and poor diet.

Supplementing meals with whey protein-enriched enteral products, which provide 3-5 g of leucine, can effectively stimulate muscle protein synthesis in older adults, potentially helping to mitigate the risk of sarcopenia during prolonged periods of inactivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mTOR1c Activation with the Leucine "Trigger" for Prevention of Sarcopenia in Older Adults During Lockdown. Mai, K., Cando, P., Trasino, SE.[2022]

A specially-formulated composition of essential amino acids (HiEAA) significantly enhances protein synthesis in older individuals with heart failure compared to a popular protein-based meal replacement (LoEAA), with more than double the anabolic response (p < 0.001).

The HiEAA formulation not only suppresses protein breakdown more effectively (p < 0.001) but also offers a low-calorie option, making it beneficial for heart failure patients who often struggle with obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consumption of a Specially-Formulated Mixture of Essential Amino Acids Promotes Gain in Whole-Body Protein to a Greater Extent than a Complete Meal Replacement in Older Women with Heart Failure. Kim, IY., Park, S., Smeets, ETHC., et al.[2020]

A systematic review of 39 randomized controlled trials involving 4274 participants found that protein and essential amino acid (EAA) supplements may improve fat-free mass, muscle strength, and physical function in older adults, particularly those who are undernourished.

Despite these potential benefits, the studies showed significant variability in results and a high risk of bias, indicating that more high-quality research is needed to establish effective nutritional strategies for maintaining strength and function in aging populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis of the effect of protein and amino acid supplements in older adults with acute or chronic conditions. Cheng, H., Kong, J., Underwood, C., et al.[2019]

Sarcopenia, a condition that increases the risk of falls and fractures in individuals over 50, can be mitigated through healthy lifestyle changes, particularly adequate dietary protein and vitamin D intake, along with regular exercise.

Optimal dietary protein intake is recommended at 1.0-1.2 g/kg body weight per day, combined with 800 IU of vitamin D daily, and engaging in physical activity 3-5 times a week to enhance muscle mass and strength effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutrition and Sarcopenia. Rizzoli, R.[2015]

A 12-week trial with 32 sedentary older men showed that combining home-based resistance exercise with a multi-ingredient supplement ('Muscle5') significantly improved muscle mass, strength, and function compared to a placebo.

The Muscle5 supplement was found to be safe and effective, particularly benefiting sarcopenic individuals, with notable increases in lean mass and fast-twitch muscle fibers, indicating enhanced muscle quality in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Five-Ingredient Nutritional Supplement and Home-Based Resistance Exercise Improve Lean Mass and Strength in Free-Living Elderly. Nilsson, MI., Mikhail, A., Lan, L., et al.[2020]

In a study involving older men aged 55-75, both a soy-dairy protein blend (PB) and whey protein isolate (WPI) effectively increased amino acid levels and activated mTORC1 signaling after resistance exercise, suggesting both can support muscle protein synthesis.

While WPI showed a significant increase in muscle protein synthesis rates and a decrease in breakdown rates, the PB did not significantly enhance these measures, indicating that while both proteins are beneficial, WPI may be more effective for muscle anabolism in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soy-Dairy Protein Blend or Whey Protein Isolate Ingestion Induces Similar Postexercise Muscle Mechanistic Target of Rapamycin Complex 1 Signaling and Protein Synthesis Responses in Older Men. Borack, MS., Reidy, PT., Husaini, SH., et al.[2021]

Older adults are at a higher risk of not getting enough dietary protein, which is crucial for maintaining muscle health, and the current recommendation of 0.8 g/kg/day may not be sufficient due to 'anabolic resistance' in aging muscles.

To effectively preserve muscle mass and function, older individuals should focus on consuming higher amounts of protein, particularly those rich in leucine or its metabolite β-hydroxy β-methylbutyrate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein Intake and Muscle Health in Old Age: From Biological Plausibility to Clinical Evidence. Landi, F., Calvani, R., Tosato, M., et al.[2022]

A 12-week study of elderly patients with chronic heart failure showed that oral amino acid supplementation significantly improved physical performance, as evidenced by increased 6-minute walk distance and maximal isometric muscular strength.

The amino acid supplementation did not adversely affect urea levels, suggesting it is a safe nonpharmacologic therapy that can enhance muscle metabolism and function in elderly patients with chronic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impairment in walking capacity and myocardial function in the elderly: is there a role for nonpharmacologic therapy with nutritional amino acid supplements? Scognamiglio, R., Testa, A., Aquilani, R., et al.[2008]

Increasing dietary protein intake above the current Recommended Dietary Allowance (RDA) of 0.8 g/kg per day may help maintain bone and muscle mass in older adults, with evidence suggesting beneficial effects at intakes of 1.0 to 1.2 g/kg per day.

Higher protein consumption (up to 1.6 to 1.8 g/kg per day) can enhance muscle and bone health by increasing insulin-like growth factor levels and calcium absorption, although long-term safety and efficacy studies are still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing dietary protein requirements in elderly people for optimal muscle and bone health. Gaffney-Stomberg, E., Insogna, KL., Rodriguez, NR., et al.[2022]

In a pilot study involving 29 patients with chronic heart failure, an oral nutritional supplement significantly increased body weight and improved quality of life over 6 weeks, with an average weight gain of 2.0 kg (3.1%) and 2.3 kg (3.6%) at 6 and 18 weeks, respectively.

The study showed that most of the weight gain was fat tissue, and there was a notable decrease in serum levels of tumor necrosis factor-α, indicating potential anti-inflammatory effects, highlighting the supplement's clinical benefits for cachectic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of a high-caloric protein-rich oral nutritional supplement in patients with chronic heart failure and cachexia on quality of life, body composition, and inflammation markers: a randomized, double-blind pilot study. Rozentryt, P., von Haehling, S., Lainscak, M., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05627440?term=NCT05627440&

A SkeleTal Muscle Recovery Intervention With Dietary ... 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 ...

2. withpower.com withpower.com/trial/phase-wastingmuscles-2023-1fee1

High-Protein Nutrition for Heart Failure-related Muscle ... Ensure Max Protein could be a promising treatment because it helps increase muscle protein, which is important for people with heart failure who often lose ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12299368/

High-Protein Dietary Interventions in Heart Failure High-protein diets offer a promising nutritional intervention to improve these outcomes in individuals with HF. Objective: This systematic review evaluated ...

4. researchgate.net researchgate.net/publication/393915061_High-Protein_Dietary_Interventions_in_Heart_Failure_A_Systematic_Review_of_Clinical_and_Functional_Outcomes

(PDF) High-Protein Dietary Interventions in Heart Failure Conclusions: High-protein dietary strategies appear to confer modest, clinically relevant gains in functional capacity, nutritional status, and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6083622/

Whey protein supplementation for the preservation of mass ... Whey protein supplementation may increase the effects of exercise on strength and muscle mass, in addition to promoting improved endothelial function, body ...

6. ensure.com ensure.com/nutrition-facts-questions-answers

Nutrition Questions & Answers Browse our frequently asked nutrition questions to see what other consumers just like you are asking about nutrition. Visit Ensure.com for more!

7. abbott.com abbott.com/corpnewsroom/nutrition-health-and-wellness/are-high-protein-diets-safe.html

Are high protein diets safe? | Abbott Newsroom If you're on the go, you should know that drinking your protein is an option. Our Ensure Max Protein shakes, which have been featured by the ...