BCAA Supplementation for TBI

(SmART-TBI Trial)

Overseen By Jonathan E Elliott, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Pregnancy, Dementia, Maple syrup urine disease, others

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using branched chain amino acids (BCAA) to improve sleep and cognitive issues, such as memory and concentration, in Veterans with mild traumatic brain injury (mTBI). The goal is to determine if BCAA can restore brain balance and alleviate these persistent symptoms. Participants will receive either BCAA supplements or a placebo (a dummy pill with no active ingredients) to compare effects. Veterans who struggle with sleep or concentration after a brain injury might be suitable for this trial, provided they aren't currently taking similar supplements or altering other sleep treatments. As an unphased trial, this study offers Veterans a unique opportunity to contribute to groundbreaking research that could lead to new treatments for mTBI-related symptoms.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are already using a sleep intervention, it must be stable and not change during the study.

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

Research has shown that branched chain amino acids (BCAAs) are generally safe for use. One study found that participants taking BCAA supplements did not encounter major safety issues. Some early research also suggests that BCAAs might help speed up recovery from concussion symptoms.

BCAAs naturally occur in protein-rich foods like meat, eggs, and dairy. Many athletes and those looking to build muscle use them as dietary supplements, which supports their safety. However, monitoring for side effects remains important, especially for individuals with traumatic brain injuries.

For those considering joining a trial, researchers will closely monitor participants for any side effects. Safety remains a top priority in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for traumatic brain injury (TBI), which often focus on managing symptoms through medications like anti-seizure drugs or diuretics, BCAA supplementation targets the brain's recovery process directly. Branched Chain Amino Acids (BCAAs) are essential nutrients that may help repair and regenerate brain tissue, potentially offering a new way to aid recovery after brain injuries. Researchers are particularly excited about BCAAs because they might improve cognitive function and reduce neurological deficits, providing a more proactive and targeted approach to healing the brain compared to traditional methods.

What evidence suggests that BCAA supplementation might be an effective treatment for mTBI?

Research has shown that branched chain amino acids (BCAAs) might aid in brain injury recovery. Studies have found that BCAA supplements can lead to moderate improvements in disability and cognitive skills. In individuals with severe brain injuries, BCAAs were linked to noticeable improvements. Early evidence from a small study suggested that BCAAs may help reduce symptoms more quickly in people with concussions. This trial will test different dosages of BCAAs—20g, 40g, and 60g daily—to evaluate their effectiveness in restoring balance in brain areas related to sleep and memory. ^{1 3 4 6 7}

Who Is on the Research Team?

Miranda M Lim, MD PhD

Principal Investigator

VA Portland Health Care System, Portland, OR

Are You a Good Fit for This Trial?

This trial is for English-speaking Veterans aged 18-65 with mild traumatic brain injury (mTBI) who experience sleep disturbances or cognitive issues. Participants must not be pregnant, have maple syrup urine disease, work night shifts, start other sleep treatments during the study, or currently use branched chain amino acids.

Inclusion Criteria

You have been diagnosed with traumatic brain injury (TBI) through a reliable interview process.

if already engaged in another sleep intervention, this must be stable and not undergo further changes during the study

Be English speaking

Exclusion Criteria

Pregnancy or female trying to conceive

You have dementia.

I am under 18 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BCAA or placebo supplementation to assess feasibility, acceptability, and limited efficacy on sleep disturbances

12 weeks

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Branched Chain Amino Acids

Trial Overview The SmART-TBI trial tests if dietary supplements with Branched Chain Amino Acids can improve sleep and cognition in mTBI patients. It's a controlled study where some get BCAAs and others a protein control to see which helps more.

How Is the Trial Designed?

Group I: BCAA 60g/daily Experimental Treatment 1 Intervention

Branched Chain Amino Acids, 30g BID x 12 weeks

Group II: BCAA 40g/daily Experimental Treatment 1 Intervention

Branched Chain Amino Acids, 20g BID x 12 weeks

Group III: BCAA 20g/daily Experimental Treatment 1 Intervention

Branched Chain Amino Acids, 10g BID x 12 weeks

Group IV: Placebo 20g/daily Placebo Group 1 Intervention

Protein without BCAA, 10g BID x 12 weeks

Branched Chain Amino Acids is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as Branched Chain Amino Acids for:

• Dietary supplement for general health and wellness

Approved in European Union as Branched Chain Amino Acids for:

• Dietary supplement for general health and wellness

Approved in Canada as Branched Chain Amino Acids for:

• Dietary supplement for general health and wellness

Approved in Japan as Branched Chain Amino Acids for:

• Dietary supplement for general health and wellness

Approved in China as Branched Chain Amino Acids for:

• Dietary supplement for general health and wellness

Approved in Switzerland as Branched Chain Amino Acids for:

• Dietary supplement for general health and wellness

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

Leucine, a branched-chain amino acid, is crucial for synthesizing brain glutamate, as it is rapidly transported across the blood-brain barrier and contributes significantly to glutamate production, with studies indicating it donates at least 25% of the amino groups for this process.

The interaction between astrocytes and neurons in the 'leucine-glutamate cycle' not only facilitates the synthesis of glutamate but also helps regulate its levels, potentially preventing excitotoxicity by buffering excess glutamate in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain metabolism of branched-chain amino acids. Yudkoff, M.[2019]

Patients with mild traumatic brain injury (TBI) showed decreased levels of branched-chain amino acids (BCAAs) compared to healthy individuals, and those with severe TBI had even lower levels, indicating a potential metabolic disruption following injury.

A combination of three altered BCAA metabolites within 24 hours post-injury could effectively predict the development of elevated intracranial pressure in severe TBI patients, suggesting that BCAA metabolism changes may play a role in TBI outcomes and could be targeted for therapeutic interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human mild traumatic brain injury decreases circulating branched-chain amino acids and their metabolite levels. Jeter, CB., Hergenroeder, GW., Ward, NH., et al.[2013]

Branched-chain amino acids (BCAA) have important pharmacologic properties that can help regulate protein synthesis and metabolism, making them beneficial in critical conditions like sepsis and liver cirrhosis.

High-dose BCAA administration in sepsis has been shown to normalize certain amino acid levels and improve metabolic abnormalities, suggesting that BCAA should be included in parenteral nutrition regimens for patients in stress conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The branched-chain amino acids]. Chiarla, C., Giovannini, I., Boldrini, G., et al.[2006]

In a 7-day study involving 101 patients with sepsis and stress, the use of a branched chain amino-acid (BCAA) enriched total parenteral nutrition (TPN) solution led to significant increases in BCAAs but caused a decrease in essential non-BCAA amino acids.

The resulting amino acid imbalance from the BCAA-enriched solution may hinder the intended anti-catabolic effects, suggesting that this formulation may not be optimal for patients requiring nutritional support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of infusion of branched chain amino-acids enriched TPN solutions on plasma amino-acid profiles in sepsis and trauma patients. Vente, JP., von Meyenfeldt, MF., van Eijk, HM., et al.[2019]

In a double-blind, placebo-controlled trial involving 126 ALS patients, branched-chain amino acids (BCAA) showed no efficacy in improving disability scales compared to placebo.

The trial was halted due to an observed excess mortality in the BCAA treatment group, raising safety concerns about the use of BCAA in ALS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Branched-chain amino acids and amyotrophic lateral sclerosis: a treatment failure? The Italian ALS Study Group. [2019]

In a controlled trial involving 32 ALS patients, treatment with branched chain amino acids (BCAA) did not show any significant clinical benefits compared to the control group.

The lack of efficacy may be attributed to the variability in ALS presentations, which can lead to unpredictable treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Branched-chain amino acids in the treatment of amyotrophic lateral sclerosis. Testa, D., Caraceni, T., Fetoni, V.[2019]

Chronic intake of a branched-chain amino acid (BCAA) or leucine-enriched diet did not show positive effects on muscle protein balance, and instead indicated negative effects from a leucine-enriched diet, particularly in fast-twitch muscles.

The study found that both diets led to increased catabolism of BCAAs, resulting in higher production of branched-chain keto acids, alanine, and glutamine, which were utilized in visceral tissues, while impairing protein synthesis in skeletal muscle during fasting states.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alterations in protein and amino acid metabolism in rats fed a branched-chain amino acid- or leucine-enriched diet during postprandial and postabsorptive states. Holecek, M., Siman, P., Vodenicarovova, M., et al.[2020]

In a study of 40 patients with severe traumatic brain injury, those who received 15 days of intravenous branched-chain amino acids (BCAAs) showed significantly greater improvement in cognitive recovery compared to a placebo group, as measured by the Disability Rating Scale.

BCAA supplementation increased plasma tyrosine levels, which are important for neurotransmitter production, while the placebo group experienced an increase in tryptophan levels, indicating that BCAAs can enhance recovery without negatively affecting these important amino acids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Branched-chain amino acids enhance the cognitive recovery of patients with severe traumatic brain injury. Aquilani, R., Iadarola, P., Contardi, A., et al.[2006]

In a study involving 50 adult mice, pre-treatment with branched-chain amino acids (BCAAs) before a traumatic brain injury (TBI) significantly improved motor recovery and cognitive function compared to untreated groups.

The best outcomes were observed in mice that received both pre- and post-treatment with BCAAs, suggesting that BCAAs may provide neuroprotective effects and support glutamate balance in the brain after injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Branched-Chain Amino Acids Are Neuroprotective Against Traumatic Brain Injury and Enhance Rate of Recovery: Prophylactic Role for Contact Sports and Emergent Use. Dickerman, RD., Williamson, J., Mathew, E., et al.[2022]

Intravenous infusion of a branched chain amino acid (BCAA)-enriched solution effectively prevented hepatic encephalopathy in rats with liver injury, keeping them from entering a coma.

The treatment increased brain BCAA levels while decreasing methionine and tyrosine levels, as well as lowering the glutamine to glutamic acid ratio, suggesting a mechanism by which BCAAs may protect brain function in liver-compromised conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of methionine and ammonia-induced coma by intravenous infusion of a branched chain amino acid solution to rats with liver injury. Shiota, T., Watanabe, A., Higashi, T., et al.[2017]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK209312/

Branched-Chain Amino Acids - Nutrition and Traumatic ... - NCBI Oral BCAAs have been examined as treatment for neurological diseases such as mania, motor malfunction, amyotrophic lateral sclerosis, and spinocerebral ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9438436/

Branched-Chain Amino Acids Are Neuroprotective Against ... Despite clinically significant improvements in severe TBI patients given BCAAs after TBI, the approach is largely an unrecognized option. Further, TBI continues ...

3. chop.edu chop.edu/news/chop-researchers-find-branched-chain-amino-acid-supplementation-may-aid-concussion-recovery

CHOP Researchers Find Branched Chain Amino Acid ... Pilot study reveals early evidence of efficacy of a pharmacologic treatment for concussion, as patients experienced faster symptom reduction ...

4. liebertpub.com liebertpub.com/doi/10.1089/neu.2023.0433

Head Injury Treatment With Healthy and Advanced Dietary ... BCAA supplementation in this population led to moderate improvement in disability and cognitive function. A single study of 18 patients (primarily adults) with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04603443

NCT04603443 | SmART-TBI: Supplementation With Amino ... Here, a novel therapy will be tested consisting of dietary supplementation with branched chain amino acids (BCAA), based on the study team's previous ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38468511/

A Pilot Randomized Controlled Trial of the Tolerability, Safety ... Although branched chain amino acid (BCAA) supplementation has shown improvements in neurocognitive and sleep function in pre-clinical animal models of mild-to- ...

7. liebertpub.com liebertpub.com/doi/10.1089/neur.2022.0031

Branched-Chain Amino Acids Are Neuroprotective Against ... They found that BCAA levels were significantly lower in TBI patients, and lower BCAA levels correlated with the severity of TBI, suggesting that BCAAs were ...