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Traumatic Brain InjurySmART-TBINCT04603443

SmART-TBI: Supplementation With Amino Acid Rehabilitative Therapy in TBI

A study testing Branched Chain Amino Acids in people with Traumatic Brain Injury, run by VA Office of Research and Development at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The most persistent and disabling postconcussive symptoms following mild traumatic brain injury (mTBI) are sleep disturbances and cognitive dysfunction, with few tractable interventions currently available. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Traumatic Brain Injury
What is being tested?
Branched Chain Amino Acids
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
175 participants
Where
1 siteUnited States
Study dates
1 Jun 2021to 30 Sep 2025
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Be Veterans (male and female; any race; 18-65 years of age)
  • Be English speaking
  • Be accessible via phone
  • Be non-decisionally impaired
  • Attest to there being no chance of being or becoming pregnant during the study (if female)
  • Attest to no history of maple syrup urine disease or known family history of maple urine syrup disease
Show all 14Show fewer
  • Have either a history of self-reported sleep disturbances, either as determined via the Insomnia Severity Index, Functional Outcomes of Sleep Questionnaire or Epworth Sleepiness Scale, clinical assessment, and/or a history of self-reported cognitive disturbance (e.g., poor memory, concentration, attention)
  • Not have an allergy to sucralose
  • Not be a shift worker (e.g. have worked night or rotating shifts more than twice in the past month)
  • Not have a diagnosis of amyotrophic lateral sclerosis
  • Not be currently supplementing their diet with branched chain amino acids
  • Not be starting another sleep intervention (e.g., positive airway pressure therapy for sleep apnea, sedative-hypnotic medication, or cognitive behavioral therapy for insomnia) during the study
  • if already engaged in another sleep intervention, this must be stable and not undergo further changes during the study
  • Meet diagnostic criteria for TBI using a validated clinical interview

Who cannot join

  • Pregnancy or female trying to conceive
  • Under 18 years old
  • Known history of maple syrup urine disease
  • Dementia

Trial locations and contacts

1 site in 1 country.

United States1 site
  • VA Portland Health Care System, Portland, OR

    Portland, Oregon, 97207-2964

Other trials in United States

About this study

Official title: Supplementation With Amino Acid Rehabilitative Therapy in TBI (SmART-TBI): A Randomized Placebo-Controlled Trial to Improve Sleep

The most persistent and disabling postconcussive symptoms following mild traumatic brain injury (mTBI) are sleep disturbances and cognitive dysfunction, with few tractable interventions currently available. Here, a novel therapy will be tested consisting of dietary supplementation with branched chain amino acids (BCAA), based on the study team's previous preclinical work showing restoration of glutamate neurotransmitter balance in sleep and memory circuits. Supplementation with Amino acid Rehabilitative Therapy in TBI (SmART-TBI) is a randomized, placebo-controlled, double-blinded, exploratory clinical trial of BCAA intended to establish the feasibility, acceptability, and limited efficacy of long-term BCAA to improve sleep and cognition in Veterans with mTBI. These results will inform the optimal study design of a future, full-scale randomized controlled trial, including the identification of the proper dose and duration of BCAA to improve sleep and the potential subpopulations of Veterans with mTBI that may benefit the most.

Read the detailed description

Mild traumatic brain injury (mTBI) has impacted over 60% of all OEF/OIF Veterans over the past decade, and over 20% of these Veterans carry a diagnosis of postconcussion syndrome. Arguably the most disabling postconcussion symptoms are sleep-wake and cognitive disturbances. Sleep, cognitive function, and related symptoms often remain impaired >10-15 years following mTBI. Not only are these symptoms themselves exceedingly difficult to live with, but poor sleep and cognition also interfere with ongoing rehabilitation interventions, and prevent reintegration into civilian life and return to gainful employment. Most existing therapies for sleep-wake and cognitive dysfunction following mTBI are merely symptomatic, and they also suffer from low efficacy and/or patient acceptability. Thus, there is an urgent need to identify mechanism-based interventions for sleep and cognitive problems following mTBI, in order to facilitate optimal rehabilitation and functional outcomes.

The study team's long-term goal is to implement a brain-bioactive pharmacological intervention to address sleep and cognitive disturbance in individuals with mTBI. The overall objective of this application, which represents the first step towards this goal, is to test the feasibility and limited efficacy of a highly promising therapy consisting of a dietary supplement, branched chain amino acids (BCAA; i.e., leucine, isoleucine, and valine), to treat sleep disturbances in individuals with mTBI. There is compelling scientific precedent and safety data to support the testing of BCAA therapy in Veterans with mTBI. Preliminary preclinical data has shown that the mechanism of action for BCAA, acting as a precursor to the excitatory neurotransmitter glutamate, restores the balance of excitation to inhibition within the dysfunctional brain circuits for both sleep and cognition in mTBI. With these data, the study team has also meticulously mapped the optimal dosing, duration, and route of administration in mice. Further, the study team now has pilot data from a double-blinded, placebo-controlled study showing that 3 weeks of dietary BCAA supplementation, but not placebo, significantly improved self-reported sleep in Veterans. Other research groups have used dietary BCAA supplementation in humans across multiple conditions at doses up to 60 grams/day and durations up to 12 months with few to no side effects.

The central hypothesis is that BCAA dietary supplementation will improve sleep quality in Veterans with mTBI. As a first step towards testing this hypothesis, herein is proposed a long-term feasibility, acceptability, and limited efficacy study of BCAA's effects on sleep that will be randomized, placebo-controlled, and double-blinded. Veterans with mTBI will be randomly assigned to receive BCAA at 20, 40 or 60 grams/day per oral (PO) or a placebo (n=50 per group) for 12 weeks. Feasibility, acceptability, and limited efficacy outcomes based on sleep (e.g., self-report, continuous actigraphy, and overnight polysomnography) will be assessed.

Results will inform the optimal study methodology and design for a future, full-scale randomized controlled trial, including the identification of the proper dose and duration of BCAA to improve sleep and the potential subpopulations of Veterans with mTBI that may be differentially affected by BCAA. This work will aos be used to generate hypotheses on the effect of BCAA on cognition and overall quality of life measures to inform future research.

Being tested
Branched Chain Amino Acids, Protein Control
Keywords
TBI, sleep, cognition, bcaa
Medical subject headings
Brain Injuries, Traumatic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Branched Chain Amino AcidsDietary supplement

    Also called BCAA-20

    Isoleucine, Leucine, and Valine, 10g BID x 12 weeks

  • Branched Chain Amino AcidsDietary supplement

    Also called BCAA-40

    Isoleucine, Leucine, and Valine, 20g BID x 12 weeks

  • Branched Chain Amino AcidsDietary supplement

    Also called BCAA-60

    Isoleucine, Leucine, and Valine, 30g BID x 12 weeks

  • Protein ControlDietary supplement

    Protein placebo control - all amino acids except for BCAA, 10g BID x 12 weeks

Study groups in NCT04603443
Study groupRoleWhat they receive
BCAA 20g/dailyExperimentalBranched Chain Amino Acids, 10g BID x 12 weeks
Receives: Dietary Supplement: Branched Chain Amino Acids
BCAA 40g/dailyExperimentalBranched Chain Amino Acids, 20g BID x 12 weeks
Receives: Dietary Supplement: Branched Chain Amino Acids
BCAA 60g/dailyExperimentalBranched Chain Amino Acids, 30g BID x 12 weeks
Receives: Dietary Supplement: Branched Chain Amino Acids
Placebo 20g/dailyPlacebo comparatorProtein without BCAA, 10g BID x 12 weeks
Receives: Dietary Supplement: Protein Control

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Patient Satisfaction With Overall Study Process

    Likert scale (1-5, higher= more satisfied) assessing satisfaction with consent process, staff, medication dispensing and regimen, devices/equipment, sleep study, questionnaires, cognitive testing, and overall experience of the study.

    Measured: 12 weeks

  2. Monitoring of Side Effects Scale (MOSES)

    Monitoring of side effects scale with emphasis on GI, neurological, psychiatric side effects. Range= 0-124, higher= more side effects.

    Measured: 4 weeks

  3. Change in Monitoring of Side Effects Scale (MOSES)

    Change in average score between week 8 and week 4 for the MOSES. The monitoring of side effects scale assesses GI, neurological, psychiatric side effects. Range= 0-124, higher= more side effects.

    Measured: 8 weeks

  4. Change in Monitoring of Side Effects Scale (MOSES)

    Change in average score between week 12 and week 4 for the MOSES. The monitoring of side effects scale assesses GI, neurological, psychiatric side effects. Range= 0-124, higher= more side effects.

    Measured: 12 weeks

  5. Reasons for Non-adherence

    Participants could select any of the following choices (multiple options allowed) to explain what prevented them from consuming the product twice a day: Side effects, Bad taste, Inconvenience, Trouble Remembering, No Time, Did not make me feel better, or Other.

    Measured: 4 weeks

  6. Reasons for Non-adherence

    Participants could select any of the following choices (multiple options allowed) to explain what prevented them from consuming the product twice a day: Side effects, Bad taste, Inconvenience, Trouble Remembering, No Time, Did not make me feel better, or Other.

    Measured: 8 weeks

  7. Reasons for Non-adherence

    Participants could select any of the following choices (multiple options allowed) to explain what prevented them from consuming the product twice a day: Side effects, Bad taste, Inconvenience, Trouble Remembering, No Time, Did not make me feel better, or Other.

    Measured: 12 weeks

  8. Recruitment Source

    Proportion of subjects recruited from various sources (clinical referral, flyers, ads, etc)

    Measured: Year 1

  9. Recruitment Source

    Proportion of subjects recruited from various sources (clinical referral, flyers, ads, etc)

    Measured: Year 2

  10. Recruitment Source

    Proportion of subjects recruited from various sources (clinical referral, flyers, ads, etc)

    Measured: Year 3

  11. Recruitment Source

    Proportion of subjects recruited from various sources (clinical referral, flyers, ads, etc)

    Measured: Year 4

  12. Recruitment

    Number of subjects randomized of those eligible as descriptive percent

    Measured: Year 1

  13. Recruitment

    Number of subjects randomized of those eligible as descriptive percent

    Measured: Year 2

  14. Recruitment

    Number of subjects randomized of those eligible as descriptive percent

    Measured: Year 3

  15. Recruitment

    Number of subjects randomized of those eligible as descriptive percent

    Measured: Year 4

  16. Study Drug Adherence by Serum

    Proportion of study drug consumed assessed by serum of BCAA.

    Measured: 12 weeks

  17. Study Drug Adherence by Sleep Diary

    Proportion of study drug consumed assessed by sleep diary.

    Measured: 12 weeks

  18. Study Drug Adherence by Drug Accounting

    Proportion of study drug consumed within each timepoint assessed by drug accounting.

    Measured: 12 weeks

  19. Actiwatch Adherence

    Proportion of days with actiwatch worn

    Measured: 12 weeks

  20. Screen Failures

    Number of enrolled participants who were later found ineligible

    Measured: From enrollment to randomization (~4 weeks)

  21. Incidence of Non-Participation

    Reason for not participating after initial contact and before consent as descriptive percent

    Measured: From first contact to declining (~1 week)

  22. Retention by Arm

    Number of participants retained by study arm

    Measured: From randomization to study completion (~12 weeks)

Secondary outcomes (1)
  1. Change in Insomnia Severity Index (ISI) From Baseline

    Change in Insomnia Severity Index (ISI) range: 0-28, higher means worse sleep

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2020
  2. Study start1 Jun 2021
  3. Primary completion30 Sep 2025
  4. Study completion30 Sep 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, double-blinded, placebo-controlled feasibility study
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
175 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04603443
Sponsor's protocol ID
NURR-003-19F
Other IDs
I01CX002022
Acronym
SmART-TBI
Status last verified
Oct 2026
First submitted
2 Oct 2020
Last updated
28 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: A limited dataset (LDS) will be created and shared pursuant to a Data Use Agreement (DUA) appropriately limiting use of the dataset and prohibiting the recipient from identifying or re-identifying any individual whose data are included in the dataset.

Questions about this trial

What is this clinical trial studying?

A study testing Branched Chain Amino Acids in people with Traumatic Brain Injury, run by VA Office of Research and Development at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Patient Satisfaction With Overall Study Process (time frame: 12 weeks). The study lists 22 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.

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