Protein Supplementation for ACL Surgery

Overseen By Haley Goble, MHA

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: The Methodist Hospital Research Institute

Must not be taking: Ergogenic aids, Protein supplements

Disqualifiers: Obesity, Diabetes, Cardiovascular disease, others

Compensation: Varies

Number of Visits: 5

Duration: 12 weeks

102 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether protein supplementation can maintain or improve muscle size after ACL surgery. Participants will receive either a protein supplement with amino acids, a whey protein isolate, or a placebo to determine which is most effective. The goal is to discover if these supplements can become a standard part of recovery after ACL reconstruction. Individuals with a recent ACL tear, scheduled for ACL surgery, and without other major health issues might be suitable for this trial. As an unphased trial, it offers participants the chance to contribute to potentially groundbreaking research in post-surgery recovery.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications known to affect protein metabolism, such as those for hormone replacement therapy or diabetes requiring insulin. If you're taking protein or amino acid supplements, you would also need to stop those.

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

Research has shown that protein and essential amino acid (EAA) supplements are generally safe for individuals recovering from leg surgeries. One study found that these supplements might enhance patients' perceptions of their recovery, although they don't appear to improve mobility.

For whey protein isolate, studies indicate it is safe and can aid in muscle growth and strength after ACL surgery. Some research suggests it might not significantly differ from not using it, but it does not seem to cause harm.

Both protein and EAA supplements are well-tolerated by patients. No serious safety issues have been reported in these studies, making them a safe option for many. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard post-ACL surgery treatment, which often involves physical therapy and pain management, the protein supplementation treatments in this trial aim to enhance recovery by focusing on muscle repair and growth. Researchers are excited about the Protein + Amino Acid Supplement Group because it combines whey protein isolate with a specific blend of amino acids like leucine and arginine, which are crucial for muscle protein synthesis and reducing recovery time. The Whey Protein Isolate Group, on the other hand, provides a straightforward protein boost that could support muscle repair without the added amino acids. These treatments offer a nutritional approach that may improve recovery outcomes more effectively than existing care options.

What evidence suggests that this trial's treatments could be effective for muscle atrophy after ACL surgery?

Research has shown that protein and essential amino acid (EAA) supplements can help reduce muscle loss after surgeries on the lower limbs, such as ACL reconstruction. In this trial, participants in the Protein + Amino Acid Supplement Group will receive a combination of whey protein isolate and an amino acid blend. Previous studies suggest this combination can improve patients' perceptions of their recovery, even if it doesn't necessarily enhance movement. Another review highlights that protein supplements can help minimize muscle loss after surgery. Participants in the Protein Supplement Group will receive whey protein isolate alone. Research on whey protein isolate has produced mixed results; some studies found it doesn't significantly increase muscle strength after ACL surgery, while others saw no extra benefits compared to a control group. Overall, protein blends with EAAs appear more promising for maintaining muscle strength after surgery. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals who have undergone ACL reconstruction surgery and are looking to prevent muscle loss during their recovery. Participants should be willing to take protein supplements or a placebo as part of the study.

Inclusion Criteria

I am between 16 and 40 years old and need surgery for a recent ACL tear.

Exclusion Criteria

I am physically unable to take part in the study activities.

Vegan patients

Rapid weight change within the past year

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a placebo, protein supplementation, or protein supplementation with amino acids twice daily for 12 weeks post-ACL reconstruction

12 weeks

4 visits (in-person) at pre-op, 4, 8, and 12 weeks post-op

Follow-up

Participants are monitored for muscle mass and patient-reported outcomes using DEXA scanning and surveys

4 weeks

1 visit (in-person) at 16 weeks post-op

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Protein + BAA
• Whey protein isolate

Trial Overview

The study is testing whether taking protein supplements (Protein + BAA, Whey protein isolate) after ACL surgery helps maintain muscle mass better than a placebo. Muscle size will be measured with DEXA scans, and participants' recovery progress will also be tracked through surveys and physical therapy results.

How Is the Trial Designed?

Group I: Protein Supplement Group Experimental Treatment 1 Intervention

Participants in this group will receive 25g of whey protein isolate twice a day for 12 weeks.

Group II: Protein + Amino Acid Supplement Group Experimental Treatment 2 Interventions

* Protein drink - 25g of whey protein isolate * Amino Acid Blend - 7g of protein (4g Leucine, 1g iso leucine, 1g valine, 1g arginine) Twice a day for 12 weeks

Group III: Placebo Group Placebo Group 1 Intervention

• isocaloric-matched (25g) maltodextrin supplement Twice a day for 12 weeks

Protein + BAA is already approved in United States, European Union for the following indications:

Approved in United States as Protein + BAA for:

• Muscle atrophy prevention post ACL reconstruction
• Nutritional support for orthopedic surgery recovery

Approved in European Union as Protein + BAA for:

• Muscle atrophy prevention post ACL reconstruction
• Nutritional support for orthopedic surgery recovery

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Published Research Related to This Trial

In a study using porcine ACL fibroblasts, it was found that a concentration of 1× platelet-rich plasma (PRP) significantly enhanced cell behaviors related to ACL healing compared to higher concentrations like 5× PRP, indicating that lower platelet concentrations may be more effective for stimulating collagen production and reducing cell death.

The research highlights the importance of platelet concentration in bio-enhanced ACL repair strategies, as 1× PRP led to the highest gene expression of type I and III collagen, improved cell metabolism, and reduced apoptosis, suggesting optimal conditions for ACL healing should be carefully considered in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing platelet concentration in platelet-rich plasma inhibits anterior cruciate ligament cell function in three-dimensional culture. Yoshida, R., Cheng, M., Murray, MM.[2021]

The modified Kennedy-MacIntosh technique for ACL reconstruction uses an 8 mm Polypropylene band to temporarily compensate for the loss of tensile strength in the autograft, which shows excellent biocompatibility and mechanical properties.

This technique promotes 'biological fixation' of the tendon-graft, which helps avoid 'stress shielding' and encourages functional adaptation through physiological stress, leading to better remodeling of the graft.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of fresh and aged cruciate ligament ruptures with combined autologous and alloplastic reinforced tendon transplant (polypropylene ligament)]. Bernett, P., Seesko, H., Feldmeier, C.[2019]

In a study of 40 patients recovering from abdominal surgery, those receiving amino acid enriched BCAA (branched-chain amino acids) showed a positive nitrogen balance two days earlier than those receiving standard amino acid nutrition, indicating faster recovery.

The BCAA group also experienced greater increases in serum total protein and albumin levels, suggesting improved nutritional status and protein synthesis compared to the standard amino acid group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of the formula of amino acids enriched BCAA on nutritional support in traumatic patients. Wang, XY., Li, N., Gu, J., et al.[2019]

The EFSA Panel concluded that whey basic protein isolate from skimmed cow's milk is safe for human consumption, including its use in infant formulas and food supplements, based on a review of its safety in 2018.

The Panel determined that extending the use of whey basic protein isolate in infant formulas and food supplements would not increase the potential intake beyond previously assessed levels, confirming its safety at these new proposed uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of whey basic protein isolate for extended uses in foods for special medical purposes and food supplements for infants pursuant to Regulation (EU) 2015/2283. Turck, D., Castenmiller, J., de Henauw, S., et al.[2020]

A study evaluating 16 protein supplements for sportspeople found that some concentrated whey protein samples had amino acid levels exceeding the European Commission's maximum tolerance by more than 20%.

In contrast, the essential and branched-chain amino acid supplements tested showed that the declared quantities matched the experimentally determined amounts, indicating better compliance in those products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proteins and protein components for sportspeople: quality control of dietary supplements. Di Stefano, V., Cicero, N., Melilli, MG., et al.[2023]

In a study involving 62 patients, the use of autologous conditioned serum (ACS) after ACL reconstruction significantly reduced bone tunnel widening compared to a placebo, with only 13% widening in the ACS group at 12 months versus 38% in the placebo group.

Patients receiving ACS also reported better clinical outcomes, including reduced stiffness and improved scores on the WOMAC and IKDC 2000 scales, alongside a significant decrease in pro-inflammatory IL-1β levels in the synovial fluid, indicating a potential mechanism for its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraarticular application of autologous conditioned serum (ACS) reduces bone tunnel widening after ACL reconstructive surgery in a randomized controlled trial. Darabos, N., Haspl, M., Moser, C., et al.[2022]

A systematic review of 6 randomized controlled trials involving 186 patients found that common dietary supplements like creatine, glucosamine, and vitamins E and C did not significantly improve muscle strength or prevent atrophy in the operated limb after ACL reconstruction.

Leucine supplementation showed a statistically significant increase in thigh circumference at 10 cm from the patella, suggesting a potential benefit for muscle hypertrophy, although overall muscle strength improvements were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of dietary supplements and whey protein on muscle mass and strength of the operated limb after anterior cruciate ligament reconstruction: a systematic review]. Lapaeva, AG., Tabakov, RS., Tabakov, SE., et al.[2023]

Preoperative isokinetic eccentric training significantly increased quadriceps strength in patients with ACL rupture, with improvements in both eccentric and concentric muscle contractions observed after 6 weeks of training.

Supplementing with whey protein isolate during the training further enhanced knee function, as indicated by a significant increase in the Lysholm score, suggesting that protein intake can boost the benefits of the training regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Preoperative Isokinetic Eccentric Training and Whey Protein Isolate Supplement on Quadriceps Strength and Knee Function in Patients with Anterior Cruciate Ligament Rupture. Zhang, XY., Huang, HS., Yang, J., et al.[2018]

Combining whey protein isolate with isokinetic eccentric training significantly increased quadriceps mass in participants with anterior cruciate ligament rupture, showing a 7.6% increase compared to no significant change in the training-only group.

Both groups improved in quadriceps strength, but only the whey protein group showed significant improvements in knee function scores, indicating potential benefits of protein supplementation in recovery, despite no statistically significant differences in strength outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of whey protein isolate and eccentric training on quadriceps mass and strength in patients with anterior cruciate ligament rupture: A randomized controlled trial. Zhang, X., Huang, H., Yu, Y., et al.[2020]

In a study of 24 patients with partial ACL ruptures, the new treatment involving trephination of the ACL origin and application of Autologous Conditioned Plasma (ACP) resulted in good to excellent clinical outcomes, with subjective scores indicating significant improvement.

The treatment had a low failure rate of 12.5%, and most patients returned to sports within an average of 4.8 months, suggesting that this technique may be a viable alternative to traditional ACL reconstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-ligamentary autologous conditioned plasma and healing response to treat partial ACL ruptures. Koch, M., Matteo, BD., Eichhorn, J., et al.[2018]

In a study of 61 patients undergoing bridge-enhanced ACL repair, it was found that higher monocyte concentrations in female patients were associated with a greater healing ligament cross-sectional area, suggesting that certain blood cell types may influence ACL healing.

Interestingly, the study revealed that physiologic platelet concentrations did not significantly affect the healing process, indicating that other factors beyond platelet levels may play a more crucial role in ACL recovery after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher Physiologic Platelet Counts in Whole Blood Are Not Associated With Improved ACL Cross-sectional Area or Signal Intensity 6 Months After Bridge-Enhanced ACL Repair. Freiberger, C., Kiapour, AM., Liu, S., et al.[2022]

Whey protein supplements from U.S. manufacturers generally contained higher levels of total protein, α-lactalbumin, β-lactoglobulin, and free branched-chain amino acids compared to those from Brazilian manufacturers, indicating better nutritional quality.

However, some brands from both the U.S. and Brazil did not meet the protein content specified on their labels, which raises concerns about the reliability of these supplements for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein and Amino Acid Profiles of Different Whey Protein Supplements. Almeida, CC., Alvares, TS., Costa, MP., et al.[2015]

In a study involving ten patients recovering from moderate surgical operations, a BCAA-enriched amino acid solution was safely administered, maintaining nitrogen equilibrium for five postoperative days without adverse effects.

The solution, which had a branched-chain to non-branched-chain amino acid ratio of 45:55%, resulted in elevated levels of branched-chain amino acids in the plasma, suggesting potential benefits for muscle recovery and nitrogen retention in postoperative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of a new branched chain--enriched amino acid solution on postoperative catabolism. Kern, KA., Bower, RH., Atamian, S., et al.[2013]

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