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

> **NIH VA I01** · PORTLAND VA MEDICAL CENTER · 2021 · —

## Abstract

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.
 Our 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 our
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. Our 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.23-26 With
these data, we have also meticulously mapped the optimal dosing, duration, and route of administration in
mice.27 Further, we now have 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.32-49
 Our central hypothesis is that BCAA dietary supplementation will improve sleep quality in Veterans with
mTBI. As a first step towards testing this hypothesis, we propose 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) wil...

## Key facts

- **NIH application ID:** 10359027
- **Project number:** 5I01CX002022-02
- **Recipient organization:** PORTLAND VA MEDICAL CENTER
- **Principal Investigator:** Miranda M Lim
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2021-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359027

## Citation

> US National Institutes of Health, RePORTER application 10359027, Supplementation with Amino Acid Rehabilitative Therapy in TBI (SmART-TBI): A Randomized Placebo-Controlled Trial to Improve Sleep (5I01CX002022-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10359027. Licensed CC0.

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