BCAA Supplements for Traumatic Brain Injury

Overseen By Miranda M Lim, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Portland VA Medical Center

Must not be taking: BCAAs

Disqualifiers: Decisional impairment, Nickel allergy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

300 Participants Needed

Trial Summary

What is the purpose of this trial?

Individuals will be recruited from the VA Portland Health Care System and the community affiliated with Oregon Health \& Science University. Traumatic brain injury status will be assessed as a contributing factor. Subjects will be randomized to one of 3 groups (BCAA or one of 2 placebo conditions) and instructed to consume study product twice daily for 21 days. Self-report questionnaires, wrist actigraphy, pressure pain testing, and cognitive function will be assessed pre and post the experimental period.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications, but you cannot participate if you are currently taking BCAA supplements.

What data supports the effectiveness of the treatment BCAA Supplements for Traumatic Brain Injury?

Research suggests that branched-chain amino acids (BCAAs) may help improve cognitive recovery in patients with severe traumatic brain injury by influencing neurotransmitter levels, which are important for brain function. ^{1 2 3 4 5}

Is it safe to use BCAA supplements for traumatic brain injury?

Some studies suggest potential safety concerns with BCAA supplements. In a trial with ALS patients, those taking BCAAs had higher mortality rates compared to those on a placebo. Additionally, high doses of leucine, a type of BCAA, can increase blood ammonia levels, which may pose health risks. ^{1 2 6 7 8}

How is the BCAA treatment for traumatic brain injury different from other treatments?

BCAA treatment for traumatic brain injury is unique because it involves the use of branched-chain amino acids, which are known to help with energy production and neurotransmitter synthesis, potentially improving cognitive recovery and sleep disturbances. Unlike other treatments, BCAAs may also offer neuroprotective benefits if taken before an injury, which could reduce the severity of the injury. ^{1 2 5 9 10}

Research Team

Miranda M Lim, MD, PhD

Principal Investigator

Portland VA Medical Center

Eligibility Criteria

This trial is for English-speaking veterans who have sleep issues after a traumatic brain injury. They must be reachable by phone. People with allergies to sucralose or nickel, decisional impairments, maple syrup urine disease (or family history of it), or those currently taking BCAAs cannot participate.

Inclusion Criteria

This criterion is too general to summarize without more context. Can you provide additional information or specify the type of sleep problems being referred to?

This criterion does not provide enough context for me to summarize it effectively. Can you please provide more information or clarify the context?

I can be reached by phone.

Exclusion Criteria

I have maple syrup urine disease or it runs in my family.

I am currently taking branched-chain amino acids (BCAAs).

I have difficulty making decisions due to a mental condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Baseline

Baseline data collection including wrist actigraphy and self-report questionnaires

4 weeks

Treatment

Participants consume study product (BCAA, rice protein, or placebo) twice daily for 21 days

3 weeks

Continuous wrist actigraphy monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive function and pressure pain testing

1 week

Treatment Details

Interventions

• Branched Chain Amino Acids

Trial Overview The study tests the effects of Branched Chain Amino Acids (BCAA) on sleep in individuals with traumatic brain injury. Participants will be randomly assigned to take either BCAA or a placebo made from microcrystalline cellulose or rice protein twice daily for three weeks.

Participant Groups

Group I: BCAAs Experimental Treatment 1 Intervention

60 grams of BCAA (2:1:1 ratio of Leucine:Isoleucine:Valine) consumed in two doses (30 grams each) mixed into 20 oz of water for up to 21 days (42 total drinks).

Group II: Rice Protein Placebo Group 1 Intervention

Rice protein control group: 60 grams of rice protein consumed in two doses (30 grams each) mixed into 20 oz of water for up to 21 days (42 total drinks).

Group III: Microcrystalline Cellulose Placebo Group 1 Intervention

Placebo control group: 60 grams of microcrystalline cellulose, consumed in two doses (30 grams each) mixed into 20 oz of water for up to 21 days (42 total drinks).

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?

Portland VA Medical Center

Lead Sponsor

Trials

44

Recruited

7,800+

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]

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]

Branched-chain amino acids (BCAAs) like leucine, isoleucine, and valine can be metabolized without relying on liver function, making them potentially beneficial supplements for patients with liver disease and encephalopathy.

BCAAs may help regulate protein synthesis, which could be advantageous in catabolic conditions such as postoperative stress and trauma, although early studies have shown mixed results regarding their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of branched-chain amino acids in liver disease, sepsis, trauma, and burns. Sax, HC., Talamini, MA., Fischer, JE.[2019]

In a study of eight patients with alcoholic liver failure, a 7-day BCAA-enriched diet led to significant clinical recovery, with seven patients reversing their encephalopathy within 3 days.

Both intravenous and nasogastric feeding improved nitrogen balance and increased the incorporation of amino acids into body proteins, indicating enhanced protein synthesis despite unchanged aromatic amino acid oxidation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enteral and parenteral branched chain amino acid-supplemented nutritional support in patients with encephalopathy due to alcoholic liver disease. O'Keefe, SJ., Ogden, J., Dicker, J.[2017]

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]

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]

The study found that acute ingestion of leucine above 500 mg/kg/day can lead to increased blood ammonia levels, indicating potential adverse effects at high intakes.

The safe upper limit for leucine intake was estimated to be around 550 mg/kg/day (approximately 39 g/day), suggesting that exceeding this amount may pose health risks, although the study focused on short-term effects rather than long-term adaptation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of the tolerable upper intake level of leucine in adult men. Pencharz, PB., Elango, R., Ball, RO.[2023]

A pilot study involving 32 Veterans with traumatic brain injury (TBI) found that dietary supplementation with branched chain amino acids (BCAA) significantly improved sleep quality, reducing insomnia symptoms and sleep latency, while being well-tolerated with minimal side effects.

The study demonstrated the feasibility and acceptability of BCAA supplementation as a potential treatment for sleep disturbances in TBI patients, suggesting that further large-scale trials are needed to confirm these preliminary findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary Supplementation With Branched Chain Amino Acids to Improve Sleep in Veterans With Traumatic Brain Injury: A Randomized Double-Blind Placebo-Controlled Pilot and Feasibility Trial. Elliott, JE., Keil, AT., Mithani, S., et al.[2023]

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]

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. Italy pubmed.ncbi.nlm.nih.gov

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

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

Clinical use of branched-chain amino acids in liver disease, sepsis, trauma, and burns. [2019]

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

Enteral and parenteral branched chain amino acid-supplemented nutritional support in patients with encephalopathy due to alcoholic liver disease. [2017]

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

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

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. 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]

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

Determination of the tolerable upper intake level of leucine in adult men. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Dietary Supplementation With Branched Chain Amino Acids to Improve Sleep in Veterans With Traumatic Brain Injury: A Randomized Double-Blind Placebo-Controlled Pilot and Feasibility Trial. [2023]

10. 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]