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

NCT04603443 | Completed DMC

• 2 other identifiers: NURR-003-19FI01CX002022
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Traumatic Brain Injury

Keywords

TBI; sleep; cognition; bcaa

Outcome Measures

Primary Outcomes (47)

• Actiwatch Adherence

  Proportion of days with actiwatch worn (goal \>70% days)

  Year 1

• Study Drug Adherence by drug accounting

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

  Year 1

• Study drug adherence by sleep diary

  Proportion of study drug consumed assessed by sleep diary.

  Year 1

• Change in Monitoring of Side Effects Scale (MOSES)

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

  12 weeks

• Study Drug Adherence by serum or sweat assay

  Proportion of study drug consumed assessed by serum or sweat assays of BCAA (goal \>70% and \>20% increase in levels.

  Year 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.

  12 weeks

• 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.

  4 weeks

• Change in Monitoring of Side Effects Scale (MOSES)

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

  8 weeks

• Reasons for non-adherence

  Likert scale questions assessing response to statements including: "It upset my stomach", "I didn't have time", "it was too much to drink", "I didn't like the taste", "I didn't feel a benefit". Scale= 0-25, higher=agree more with statement.

  4 weeks

• Change in Reasons for non-adherence

  Change in Likert scale questions assessing response to statements including: "It upset my stomach", "I didn't have time", "it was too much to drink", "I didn't like the taste", "I didn't feel a benefit". Scale= 0-25, higher=agree more with statement.

  8 weeks

• Change in Reasons for non-adherence

  Change in Likert scale questions assessing response to statements including: "It upset my stomach", "I didn't have time", "it was too much to drink", "I didn't like the taste", "I didn't feel a benefit". Scale= 0-25, higher=agree more with statement.

  12 weeks

• Recruitment

  Number of subjects consented of those eligible as descriptive percent

  Year 1

• Recruitment source

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

  Year 1

• Retention

  Number of completers out of the total number consented as descriptive statistic

  Year 1

• Retention by arm

  Proportion of drop out within each arm

  Year 1

• Incidence of non-participation

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

  Year 1

• Screen Failures

  Number of subjects enrolled who were later found ineligible as a descriptive percent

  Year 1

• Screen Failures

  Number of subjects enrolled who were later found ineligible as a descriptive percent

  Year 2

• Screen Failures

  Number of subjects enrolled who were later found ineligible as a descriptive percent

  Year 3

• Screen Failures

  Number of subjects enrolled who were later found ineligible as a descriptive percent

  Year 4

• Incidence of non-participation

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

  Year 2

• Incidence of non-participation

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

  Year 3

• Incidence of non-participation

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

  Year 4

• Retention by arm

  Proportion of drop out within each arm

  Year 2

• Retention by arm

  Proportion of drop out within each arm

  Year 3

• Retention by arm

  Proportion of drop out within each arm

  Year 4

• Retention

  Number of completers out of the total number consented as descriptive statistic

  Year 2

• Retention

  Number of completers out of the total number consented as descriptive statistic

  Year 3

• Retention

  Number of completers out of the total number consented as descriptive statistic

  Year 4

• Recruitment source

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

  Year 2

• Recruitment source

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

  Year 3

• Recruitment source

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

  Year 4

• Recruitment

  Number of subjects consented of those eligible as descriptive percent

  Year 2

• Recruitment

  Number of subjects consented of those eligible as descriptive percent

  Year 3

• Recruitment

  Number of subjects consented of those eligible as descriptive percent

  Year 4

• Study Drug Adherence by serum or sweat assay

  Proportion of study drug consumed assessed by serum or sweat assays of BCAA (goal \>70% and \>20% increase in levels.

  Year 2

• Study drug adherence by serum or sweat assay

  Proportion of study drug consumed assessed by serum or sweat assays of BCAA (goal \>70% and \>20% increase in levels.

  Year 3

• Study drug adherence by serum or sweat assay

  Proportion of study drug consumed assessed by serum or sweat assays of BCAA (goal \>70% and \>20% increase in levels.

  Year 4

• Study Drug Adherence by sleep diary

  Proportion of study drug consumed assessed by sleep diary.

  Year 2

• Study Drug Adherence by sleep diary

  Proportion of study drug consumed assessed by sleep diary.

  Year 3

• Study Drug Adherence by sleep diary

  Proportion of study drug consumed assessed by sleep diary.

  Year 4

• Study drug adherence by drug accounting

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

  Year 2

• Study drug adherence by drug accounting

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

  Year 3

• Study drug adherence by drug accounting

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

  Year 4

• Actiwatch Adherence

  Proportion of days with actiwatch worn (goal \>70% days)

  Year 2

• Actiwatch Adherence

  Proportion of days with actiwatch worn (goal \>70% days)

  Year 3

• Actiwatch Adherence

  Proportion of days with actiwatch worn (goal \>70% days)

  Year 4

Study Arms (4)

BCAA 20g/daily

EXPERIMENTAL

Branched Chain Amino Acids, 10g BID x 12 weeks

Dietary Supplement: Branched Chain Amino Acids

BCAA 40g/daily

EXPERIMENTAL

Branched Chain Amino Acids, 20g BID x 12 weeks

Dietary Supplement: Branched Chain Amino Acids

BCAA 60g/daily

EXPERIMENTAL

Branched Chain Amino Acids, 30g BID x 12 weeks

Dietary Supplement: Branched Chain Amino Acids

Placebo 20g/daily

PLACEBO COMPARATOR

Protein without BCAA, 10g BID x 12 weeks

Dietary Supplement: Protein Control

Interventions

Branched Chain Amino Acids DIETARY_SUPPLEMENT

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

Also known as: BCAA-20

BCAA 20g/daily

Protein Control DIETARY_SUPPLEMENT

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

Placebo 20g/daily

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

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

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Children's Hospital of Philadelphia: collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97207-2964, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Amino Acids

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Amino Acids, Peptides, and Proteins

Study Officials

• Miranda M Lim, MD PhD

  VA Portland Health Care System, Portland, OR

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Both participants and study team members will be double blinded to intervention. The biostatistician and Research Pharmacist dispensing drug will be the only ones with the key to unblinding.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Randomized, double-blinded, placebo-controlled feasibility study

Study Record Dates

• First Submitted: October 2, 2020
• First Posted: October 26, 2020
• Study Start: June 1, 2021
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: January 6, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 6 months after the resulting publication
• Access Criteria: Final datasets will be maintained locally until institutional resources become available for public access to data sets. Limited de-identified data sets will be made available on a case-by-case basis in response to specific user requests that meet criteria specified above.

Locations

US (1)