High-Protein Nutrition for Heart Failure-related Muscle Wasting

(ASTRID-HF Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Tufts Medical Center

Disqualifiers: Pregnancy, LVAD, Cancer, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing whether protein supplements can help patients with heart failure who are losing muscle. The study will compare different amounts of protein to see if it helps build muscle in these patients. Researchers believe that extra protein might counteract the body's muscle-wasting processes.

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.

What data supports the idea that High-Protein Nutrition for Heart Failure-related Muscle Wasting is an effective treatment?

The available research shows that high-protein nutrition can be effective for heart failure-related muscle wasting. In a study with patients suffering from chronic heart failure and cachexia, those who received a high-protein supplement gained weight and improved their quality of life. Specifically, 19 out of 20 patients gained weight after 6 weeks, and 17 out of 19 maintained this gain after 18 weeks. Additionally, there was a significant improvement in their quality of life. This suggests that high-protein nutrition can help improve body weight and overall well-being in these patients. ^{1 2 3 4 5}

What safety data exists for high-protein nutrition in treating muscle wasting in heart failure?

The research indicates that high-protein nutrition, particularly with leucine-enriched supplements, is generally safe and beneficial for older adults experiencing muscle wasting. Whey protein-enriched supplements are commonly used in clinical settings to preserve lean body mass. Studies suggest that increasing dietary protein intake above the current RDA may help maintain muscle mass in older individuals without adverse effects on renal function. However, long-term studies are needed to confirm the safety and efficacy of these supplements. ^{1 4 6 7 8}

Is Ensure Max Protein a promising treatment for muscle wasting in heart failure patients?

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 muscle. It provides essential nutrients that can help maintain or improve muscle mass. ^{1 6 9 10 11}

Research Team

Eligibility Criteria

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.

I am between 18 and 100 years old.

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.

Trial Timeline

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)

Treatment Details

Interventions

• Ensure Max Protein (Protein Supplementation)
• Ensure Original (Protein Supplementation)

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.

Participant Groups

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 Canada for the following indications:

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+

Michael Dandorph

Tufts Medical Center

Chief Executive Officer since 2022

MBA

Helen Boucher

Tufts Medical Center

Chief Medical Officer since 2022

MD, FACP, FIDSA

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Dr. Gary H. Gibbons

National Heart, Lung, and Blood Institute (NHLBI)

Chief Executive Officer since 2012

MD from Harvard Medical School

Dr. James P. Kiley

National Heart, Lung, and Blood Institute (NHLBI)

Chief Medical Officer since 2011

MD from University of California, San Francisco

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

References

1. England 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. [2019]

2. Switzerland 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. [2023]

3. Germany 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. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Protein Intake and Muscle Health in Old Age: From Biological Plausibility to Clinical Evidence. [2022]

5. United States 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? [2008]

6. United States pubmed.ncbi.nlm.nih.gov

mTOR1c Activation with the Leucine "Trigger" for Prevention of Sarcopenia in Older Adults During Lockdown. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A Five-Ingredient Nutritional Supplement and Home-Based Resistance Exercise Improve Lean Mass and Strength in Free-Living Elderly. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Increasing dietary protein requirements in elderly people for optimal muscle and bone health. [2022]

9. Switzerland 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. [2020]

10. United States 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. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Nutrition and Sarcopenia. [2015]