High Protein Diet + Exercise for Muscle Loss

(PROXIMUS Trial)

Recruiting at 1 trial location

Overseen By Lori Bechard, RD, PhD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Boston Children's Hospital

Disqualifiers: Liver failure, Kidney failure, ECMO, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 10 days

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The investigators have designed a 2-center, pilot feasibility, randomized controlled trial (PROXIMUS) to determine the feasibility and safety of a larger multi center, randomized open-label trial comparing high protein combined with individualized exercise vs. standard management during the acute phase of critical illness in children. The investigators aim to determine the impact of the intervention on preservation of muscle mass; and functional status at 1 month and 6 months after randomization.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is a high protein diet with exercise safe for humans?

Research shows that protein supplements, including whey protein, are generally safe for humans when combined with exercise, even in older adults. These studies have not reported significant safety concerns, suggesting that this combination is well-tolerated. ^{1 2 3 4 5}

How does the High Protein Diet + Exercise treatment differ from other treatments for muscle loss?

This treatment is unique because it combines a high protein diet with individualized exercise prescriptions, which may enhance muscle mass and function more effectively than protein or exercise alone. The focus on personalized exercise plans and specific protein intake timing and dosage sets it apart from standard approaches. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment High Protein Diet + Exercise for Muscle Loss?

Research shows that high protein diets and exercise can help maintain muscle mass in older adults and those experiencing muscle loss due to conditions like sarcopenia (age-related muscle loss) and cachexia (muscle wasting). Protein supplements, especially when combined with resistance exercise, have been found to improve muscle mass and strength. ^{1 2 5 11 12}

Who Is on the Research Team?

Nilesh Mehta, MD

Principal Investigator

Faculty, Boston Children's Hospital

Sapna R Kudchadkar, MD

Principal Investigator

Faculty, Johns Hopkins

Are You a Good Fit for This Trial?

This trial is for children aged 1 to under 18 years who are on mechanical ventilation within the first 48 hours of PICU admission and expected to stay on it. They must be able to consent within this period. It's not for those with liver failure, certain medical conditions requiring bedrest, high-risk burns, severe kidney issues without therapy, or incompatible diets.

Inclusion Criteria

I am between 1 and 17 years old, corrected for prematurity.

I needed a breathing tube within the first 48 hours of ICU admission and will need it for at least 2 more days.

Able to consent to participate within 48 hours of initiation of mechanical ventilation initiation.

Exclusion Criteria

My kidney function is severely reduced and I am not on dialysis.

I have a genetic disorder that affects my metabolism.

I have severe burns covering a large part of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high protein combined with individualized exercise or standard management during the acute phase of critical illness

10 days

Daily monitoring during PICU stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments at 1 and 6 months

6 months

Assessments at 1 month and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Protein dosage and rehabilitation team delivered exercise prescription

Trial Overview The PROXIMUS study tests if giving high protein with tailored exercise during critical illness helps maintain muscle mass and improve mobility in kids after treatment. Participants will either receive this new approach or standard care, decided randomly at two centers.

How Is the Trial Designed?

Group I: High protein plus exercise Experimental Treatment 1 Intervention

High protein nutrition: To achieve the prescribed age-appropriate high protein target, dietitians will use EN preferentially, or if EN is contraindicated, PN may be used. High-protein EN formulas and/or protein supplements (powder or liquid) will be added to formula/breast milk feedings or administered separately in divided bolus doses. Dietitians routinely employ and customize these solutions in their scope of practice. When EN is insufficient to meet protein targets, PN may be prescribed to make up the deficit on or after the end of PICU day 3. Energy and protein delivery adequacy (% of prescribed goal) will be monitored daily by the study team. Patients in this arm will also be prescribed the age-appropriate highest-level of mobility by the rehabilitation team with a goal of 30 minutes duration, twice daily.

Group II: Standard protein and exercise Active Control 1 Intervention

All enrolled patients randomized to this arm will receive a baseline nutrition and nurse-driven mobility pathway and other evidence-based bundled strategies as standard of care.

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Published Research Related to This Trial

Dietary protein supplementation of more than 1.5 g/kg per day may help maintain or improve muscle mass in patients with cachexia, especially when combined with exercise training.

However, there is still a lack of clinical studies directly linking protein intake to muscle weight gain and function, highlighting the need for more research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Muscle atrophy in cachexia: can dietary protein tip the balance? Op den Kamp, CM., Langen, RC., Haegens, A., et al.[2011]

Whey protein supplementation during resistance exercise training (RET) in older adults with sarcopenia showed a small but significant increase in skeletal muscle mass and handgrip strength compared to RET without whey protein or with a placebo, based on a review of seven trials involving 591 participants.

Despite these positive findings, the overall effect sizes were small and did not exceed the minimally important clinical difference, indicating that while whey protein may help, the clinical significance of the improvements is limited and further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Whey Protein Supplementation during Resistance Exercise Training on Skeletal Muscle Mass and Strength in Older People with Sarcopenia: A Systematic Review and Meta-Analysis. Cuyul-Vásquez, I., Pezo-Navarrete, J., Vargas-Arriagada, C., et al.[2023]

Multi-ingredient protein (MIP) supplements, when combined with resistance training, significantly increased fat-free mass (0.80 kg) and strength (4.22 kg for lower body and 2.56 kg for upper body) compared to non-MIP supplements across 35 trials with 1387 participants.

The benefits of MIP supplements were particularly pronounced in untrained individuals and older adults, showing greater gains in muscle mass and strength compared to those who were already trained or younger, although MIP was not superior to protein-only supplements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do multi-ingredient protein supplements augment resistance training-induced gains in skeletal muscle mass and strength? A systematic review and meta-analysis of 35 trials. O'Bryan, KR., Doering, TM., Morton, RW., et al.[2022]

In a study involving 100 overweight and obese older adults over 10 weeks, a high protein diet alone did not significantly preserve fat-free mass (FFM) during weight loss, but when combined with resistance exercise, it led to a significant increase in FFM by 0.6 kg.

The research indicates that while a high protein diet alone may not be effective in preventing muscle loss during weight loss, combining it with resistance exercise can enhance muscle preservation in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a high protein diet and/or resistance exercise on the preservation of fat free mass during weight loss in overweight and obese older adults: a randomized controlled trial. Verreijen, AM., Engberink, MF., Memelink, RG., et al.[2022]

In a study involving 15 overweight men, it was found that during a severe energy deficit, whey protein ingestion did not enhance muscle mass preservation due to the body's reduced responsiveness to anabolic signals, despite exercise.

The research highlighted that hormonal changes, such as decreased insulin and testosterone and increased cortisol, were linked to the inability of muscle to effectively utilize protein for growth during extreme caloric restriction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein synthesis signaling in skeletal muscle is refractory to whey protein ingestion during a severe energy deficit evoked by prolonged exercise and caloric restriction. Martin-Rincon, M., Perez-Suarez, I., Pérez-López, A., et al.[2020]

In elderly men, consuming 20 grams of whey protein significantly increases muscle protein synthesis (MPS) above fasting levels, while higher doses (40 grams) further enhance MPS, especially after resistance exercise.

Unlike younger adults, older adults benefit from higher protein doses post-exercise, indicating that their muscles continue to respond positively to increased protein intake even beyond the typical saturation point seen in younger individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. Yang, Y., Breen, L., Burd, NA., et al.[2022]

In a study involving 31 older adults (ages 60 to 80) undergoing 12 weeks of resistance training, both whey protein supplementation and a placebo resulted in similar improvements in muscle strength and mass, indicating that additional protein did not enhance the effects of resistance training.

Participants showed significant increases in muscle thickness and functional capacity, as measured by sit-to-stand and timed-up-and-go tests, regardless of whether they received whey protein or placebo, suggesting that resistance training alone is effective for improving these parameters in older individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can supplemental protein to low-protein containing meals superimpose on resistance-training muscle adaptations in older adults? A randomized clinical trial. de Azevedo Bach, S., Radaelli, R., Beck Schemes, M., et al.[2022]

Higher protein intakes (1.6-2.4 g/kg/day) during weight loss are recommended for athletes to help preserve muscle mass while losing fat, which is crucial for maintaining performance.

The effectiveness of protein intake for weight loss in athletes can be influenced by factors such as the severity of caloric deficit, type of training, and the timing and quality of protein consumed throughout the day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein Recommendations for Weight Loss in Elite Athletes: A Focus on Body Composition and Performance. Hector, AJ., Phillips, SM.[2018]

In a study involving 18 young untrained males, those who took a 25.1 g protein complex supplement before and after resistance exercise training (RET) showed significant improvements in muscular function compared to those who received a placebo.

The protein supplement group demonstrated enhanced isokinetic performance, particularly in leg extension and flexion, indicating that combining protein supplementation with RET can lead to better muscle function outcomes over a 12-week period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The synergistic effect of protein complex supplementation combined with 12 weeks of resistance training on isokinetic muscular function in untrained young males. Jang, J., Park, HY., Yoo, C., et al.[2020]

A study involving 12 resistance-trained males found that different feeding patterns of whey protein before exercise can alter plasma amino acid profiles and post-exercise signaling, but do not affect the overall muscle protein synthesis (MPS) response after exercise.

Both rapidly and slowly digested proteins, when consumed in sufficient amounts before resistance exercise, equally enhance MPS, indicating that the timing of protein intake may not be as critical as previously thought.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preexercise aminoacidemia and muscle protein synthesis after resistance exercise. Burke, LM., Hawley, JA., Ross, ML., et al.[2022]

Regular exercise increases protein requirements for active individuals, with strength or speed athletes needing about 1.2-1.7 g of protein per kg of body weight per day, and endurance athletes requiring about 1.2-1.4 g/kg/day.

Current evidence suggests that consuming these higher protein amounts (100-212% of standard recommendations) is safe and can be achieved with a diet comprising 12-15% of energy from protein, although more research is needed to refine these guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of exercise on protein requirements. Lemon, PW.[2005]

In a study of 27 untrained healthy young adults, both whey and soy protein supplementation during 6 weeks of resistance training significantly increased lean tissue mass and strength compared to a placebo.

The results suggest that while protein supplementation is beneficial, the type of protein (whey vs. soy) does not significantly impact the outcomes in terms of lean tissue mass and strength gains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of whey and soy protein supplementation combined with resistance training in young adults. Candow, DG., Burke, NC., Smith-Palmer, T., et al.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Muscle atrophy in cachexia: can dietary protein tip the balance? [2011]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of Whey Protein Supplementation during Resistance Exercise Training on Skeletal Muscle Mass and Strength in Older People with Sarcopenia: A Systematic Review and Meta-Analysis. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Do multi-ingredient protein supplements augment resistance training-induced gains in skeletal muscle mass and strength? A systematic review and meta-analysis of 35 trials. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Effect of a high protein diet and/or resistance exercise on the preservation of fat free mass during weight loss in overweight and obese older adults: a randomized controlled trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Protein synthesis signaling in skeletal muscle is refractory to whey protein ingestion during a severe energy deficit evoked by prolonged exercise and caloric restriction. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Can supplemental protein to low-protein containing meals superimpose on resistance-training muscle adaptations in older adults? A randomized clinical trial. [2022]

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

Protein Recommendations for Weight Loss in Elite Athletes: A Focus on Body Composition and Performance. [2018]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

The synergistic effect of protein complex supplementation combined with 12 weeks of resistance training on isokinetic muscular function in untrained young males. [2020]

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

Preexercise aminoacidemia and muscle protein synthesis after resistance exercise. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Effect of exercise on protein requirements. [2005]

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

Effect of whey and soy protein supplementation combined with resistance training in young adults. [2022]