BCAA Supplementation for TBI

(SmART-TBI Trial)

Overseen by Miranda M Lim, MD PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: VA Office of Research and Development

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

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests a dietary supplement called BCAA to help Veterans with mild traumatic brain injury improve their sleep and cognitive function. BCAA helps balance a brain chemical important for these functions. The study aims to see if BCAA is effective and safe over time. BCAA supplementation has shown promise in improving outcomes for severe TBI, but its benefits for mild TBI are not yet well-established.

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.

What evidence supports the effectiveness of BCAA supplementation as a treatment for traumatic brain injury (TBI)?

Research suggests that branched-chain amino acids (BCAAs) may help improve cognitive recovery in patients with severe TBI and could be neuroprotective, potentially reducing the severity of injury if taken before TBI. BCAAs are involved in energy production and neurotransmitter synthesis, which are important for brain function and recovery. ^{1 2 3 4 5}

Is BCAA supplementation safe for humans?

In a study on amyotrophic lateral sclerosis (ALS) patients, BCAA supplementation was linked to higher mortality, leading to the trial's early termination. However, BCAAs are generally considered safe in other contexts, such as muscle protein balance and certain critical conditions, but their safety in traumatic brain injury (TBI) specifically is not well-documented. ^{1 3 6 7 8}

How is the BCAA treatment for TBI different from other treatments?

The BCAA treatment for TBI is unique because it focuses on supplementing branched-chain amino acids, which are crucial for energy production and neurotransmitter synthesis in the brain. This approach aims to address the decreased levels of BCAAs observed in TBI patients, potentially improving cognitive recovery and reducing TBI pathology. ^{1 3 4 9 10}

Research Team

Miranda M Lim, MD PhD

Principal Investigator

VA Portland Health Care System, Portland, OR

Eligibility Criteria

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

I am under 18 years old.

You have dementia.

Trial Timeline

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

Treatment Details

Interventions

• Branched Chain Amino Acids (Amino Acid Therapy)

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.

Participant Groups

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 Canada, Japan, China, Switzerland for the following indications:

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+

Dr. Grant Huang

VA Office of Research and Development

Acting Chief Research and Development Officer

PhD in Medical Psychology and Master of Public Health from the Uniformed Services University of Health Sciences

Dr. Erica M. Scavella

VA Office of Research and Development

Chief Medical Officer since 2022

MD from University of Massachusetts School of Medicine

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Joseph W. St. Geme III

Children's Hospital of Philadelphia

Chief Medical Officer since 2021

MD, PhD, MPH

Madeline Bell

Children's Hospital of Philadelphia

Chief Executive Officer since 2015

BSc in Nursing from Villanova University, MSc in Organizational Dynamics from the University of Pennsylvania

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

John Hunter

Oregon Health and Science University

Chief Medical Officer since 2024

MD, specific details unavailable

Ann Madden Rice

Oregon Health and Science University

Chief Executive Officer

FACHE certification, extensive leadership experience in academic health centers

Findings from Research

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]

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]

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 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 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]

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]

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]

References

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

Human mild traumatic brain injury decreases circulating branched-chain amino acids and their metabolite levels. [2013]

2. England 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. [2019]

3. Italy pubmed.ncbi.nlm.nih.gov

[The branched-chain amino acids]. [2006]

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

Branched-chain amino acids enhance the cognitive recovery of patients with severe traumatic brain injury. [2006]

5. United States 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. [2022]

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

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

7. Germany pubmed.ncbi.nlm.nih.gov

Branched-chain amino acids in the treatment of amyotrophic lateral sclerosis. [2019]

8. England 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. [2020]

9. Japan 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. [2017]

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

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