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Concussion, BrainPhase 2NCT06829498

BCAAs in Concussion 2.0

A Phase 2 study testing BCAA in people with Concussion, Brain and Concussion, Mild, run by Akiva Cohen 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

This study is a randomized, placebo-controlled, double-blinded, therapeutic exploratory clinical trial of branched chain amino acids (BCAAs) in the treatment of concussion. The aim of the study is to determine whether administration of high-dose BCAAs compared to placebo promotes concussion recovery. Read more about this study

Who is it for?
Ages 11 to 23 years
Conditions the study is for
Concussion, Brain, Concussion, Mild, Concussion
What is being tested?
BCAA
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
17 participants
Where
1 siteUnited States
Study dates
1 Apr 2025to 1 Jul 2026
Phase
Phase 2
Are there results?
None posted in the registry

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 11 to 23 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Males and females,11 - 23 years of age.
  • Weigh at least 40kg.
  • Meeting concussion criteria for the American Congress of Rehabilitative Medicine.
  • Present within 4 days of injury.
  • Post-menarchal females must have a negative urine pregnancy test and must use an acceptable method of contraception.
  • Informed consent by the participant, or for participants <18 years old both informed consent by a parent/guardian and child assent.

Who cannot join

  • Evidence of moderate or severe Traumatic Brain Injury (TBI), including Glasgow Coma Scale (GCS) <13, TBI requiring hospital admission, or TBI requiring neurosurgical intervention.
  • Prior concussion or TBI within 90 days.
  • Known history of maple syrup urine disease or known family history of maple syrup urine disease.
  • Any investigational drug use within 30 days prior to enrollment.
  • Hypersensitivity to any ingredient in the active or placebo products.
  • Participants who are pregnant, planning on becoming pregnant during the study duration, or breastfeeding.
  • Non-English speaking participants or parent/guardian.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19146

Other trials in United States

About this study

Official title: HIT HEADS 2.0: Head Injury Treatment: A Randomized, Placebo-controlled, Double-blinded, Therapeutic Clinical Trial of Branched Chain Amino Acids (BCAAs) in the Treatment of Concussion

This study is a randomized, placebo-controlled, double-blinded, therapeutic exploratory clinical trial of branched chain amino acids (BCAAs) in the treatment of concussion. The aim of the study is to determine whether administration of high-dose BCAAs compared to placebo promotes concussion recovery.

Read the detailed description

Annually, approximately 2 million concussions occur in the pediatric and young adult population. Approximately 30% of those diagnosed with concussion will experience persisting symptoms lasting beyond 28 days. Concussion is a heterogeneous injury to the brain that precipitates a complex pathophysiological process that can result in a cascade of deleterious side effects. At present, there are no targeted therapeutics that can mitigate or prevent the deleterious effects of concussion. In preclinical, analysis of ipsilateral hippocampi isolated from mice after traumatic brain injury (TBI) demonstrated that only the concentrations of the three branched chain amino acids (BCAAs) (valine, isoleucine, and leucine) were significantly reduced after injury. When these brain-injured animals received dietary supplementation with BCAAs, the concentrations of these amino acids were restored in the injured hippocampus and the injured animals demonstrated significant cognitive improvement to levels comparable to those obtained in non-injured control animals. The pilot study (NCT01860404) provides evidence of BCAAs in concussed adolescents and young adults providing a dose-response effect in reducing concussion symptoms and a return to baseline physical activity in those treated with higher total doses of BCAAs, warranting this larger trial to inform clinical practice around BCAA treatment in concussion.

Being tested
BCAA, Placebo
Medical subject headings
Brain Concussion

What participants receive

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

  • BCAADrug

    The three BCAAs will be combined together and dissolved in a flavored solution.

  • PlaceboOther

    The placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.

Study groups in NCT06829498
Study groupRoleWhat they receive
Drug: Branched Chain Amino AcidsExperimentalThe three BCAAs will be combined together and dissolved into a flavored solution.
Receives: Drug: BCAA
PlaceboPlacebo comparatorThe placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.
Receives: Other: Placebo

What is being measured

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

  1. Number of participants that have met have met criteria for recovery at 28 days post-injury, defined as return to baseline symptom levels along with feeling > 90% back to normal.

    This will be determined by research staff at in person visits by the return to baseline symptom levels along with participant self-report of feeling > 90% back to normal. Percentage recovered at 28 days will be compared between placebo and control group by chi-square testing.

    Measured: 28 days

Secondary outcomes (13)
  1. Determine whether administration of high-dose BCAAs (54g/day) compared to placebo supplementation, promotes concussion recovery operationalized by the return to baseline (pre-injury) concussion symptom levels.

    This will be determined by a comparison of total score on the Post-concussion Symptom Scale (PCSS) (22 symptoms each rated on a 0-6 Likert scale, total scale of 0-132). A participant is deemed recovered when total score is within 3 points of their pre-injury score, time to recovery will be compared among placebo and control groups by Wilcoxon rank sum test.

    Measured: 28 days

  2. Determine whether administration of BCAAs leads to a lower visio-vestibular abnormality burden compared to placebo.

    This will be determined by the visio-vestibular examination (VVE) score, a score of 0-9 based on accumulation of abnormalities on the nine elements of the VVE. Average VVE score will be compared among placebo and control groups by Wilcoxon rank sum tests.

    Measured: 28 days

  3. Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities--maximum pupil diameter compared to placebo.

    This will be determined by a comparison of the average maximum pupil diameter (measured in mm, scale 0-9 mm) between placebo and control using Wilcoxon rank sum test, whereby larger pupil diameter represents an abnormality.

    Measured: 28 days

  4. Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities--minimum pupil diameter compared to placebo.

    This will be determined by a comparison of the average minimum pupil diameter (measured in mm, scale 0-9 mm) between placebo and control using Wilcoxon rank sum test, whereby larger pupil diameter represents an abnormality.

    Measured: 28 days

  5. Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-percentage of pupil constriction compared to placebo.

    This will be determined by a comparison of the average percentage of pupil constriction change (measured in %, scale 0-100) between placebo and control using Wilcoxon rank sum test, whereby larger percent represents an abnormality.

    Measured: 28 days

  6. Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-constriction latency compared to placebo.

    This will be determined by a comparison of the average constriction latency (measured in ms, scale 0-1000 ms) between placebo and control using Wilcoxon rank sum test, whereby shorter latency represents an abnormality.

    Measured: 28 days

  7. Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-average constriction velocity compared to placebo.

    This will be determined by a comparison of the median average constriction velocity (measured in mm/s, scale 0-5 mm/s) between placebo and control using Wilcoxon rank sum test, whereby faster constriction velocity represents an abnormality.

    Measured: 28 days

  8. Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities--peak constriction velocity compared to placebo.

    This will be determined by a comparison of the average peak constriction velocity (measured in mm/s, scale 0-5 mm/s) between placebo and control using Wilcoxon rank sum test, whereby faster constriction velocity represents an abnormality.

    Measured: 28 days

  9. Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-average dilation velocity compared to placebo.

    This will be determined by a comparison of the median average dilation velocity (measured in mm/s, scale 0-5 mm/s) between placebo and control using Wilcoxon rank sum test, whereby faster dilation velocity represents an abnormality.

    Measured: 28 days

  10. Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-peak dilation velocity compared to placebo.

    This will be determined by a comparison of the average peak dilation velocity (measured in mm/s, scale 0-5 mm/s) between placebo and control using Wilcoxon rank sum test, whereby faster velocity represents an abnormality.

    Measured: 28 days

  11. Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-T75 compared to placebo.

    This will be determined by a comparison of the average time to reach 75% of the original baseline pupil diameter (T75) after peak constriction (measured in s, scale 0-4 s) between placebo and control using Wilcoxon rank sum test, whereby faster time represents an abnormality.

    Measured: 28 days

  12. Determine whether administration of BCAAs leads to subjective improvement in sleep quality compared to placebo.

    Sleep quality will be determined by utilization of the PROMIS sleep questionnaire with 8 questions and a 5 point scale (1- not at all, 2- a little bit, 3- somewhat, 4- quite a bit and 5- very much). The PROMIS Sleep Disturbance score is calculated by adding up the raw scores for each item on the PROMIS Sleep Disturbance scale. The score is then rescaled to a standardized T-score using a conversion table. A higher score indicates greater sleep disturbance. Total range of score is 8-40. Average score will be compared between placebo and control using Wilcoxon rank sum test.

    Measured: 28 days

  13. Determine whether administration of BCAAs leads to subjective improvement in physical activity compared to placebo.

    Physical activity will be determined by utilization of the PROMIS sleep questionnaire with 8 questions and an aggregate score of X. Physical activity will be determined by utilization of the PROMIS Physical Activity questionnaire with 8 questions and a 5 point scale (1- not at all, 2- a little bit, 3- somewhat, 4- quite a bit and 5- very much). A higher aggregate score may be indicative of greater activity limitations or reduced activity levels. Total range of score is 8-40. Average score will be compared between placebo and control using Wilcoxon rank sum test.

    Measured: 28 days

Timeline

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

  1. First posted17 Feb 2025
  2. Study start1 Apr 2025
  3. Primary completion31 Dec 2025
  4. Study completion1 Jul 2026

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06829498
Sponsor's protocol ID
23-021206
Status last verified
Sep 2026
First submitted
30 Jan 2025
Last updated
3 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Corwin DJ, Myers SR, Arbogast KB, Lim MM, Elliott JE, Metzger KB, LeRoux P, Elkind J, Metheny H, Berg J, Pettijohn K, Master CL, Kirschen MP, Cohen AS. Head Injury Treatment With Healthy and Advanced Dietary Supplements: A Pilot Randomized Controlled Trial of the Tolerability, Safety, and Efficacy of Branched Chain Amino Acids in the Treatment of Concussion in Adolescents and Young Adults. J Neurotrauma. 2024 Jun;41(11-12):1299-1309. doi: 10.1089/neu.2023.0433. Epub 2024 Apr 11.

    PubMed 38468511

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BCAA in people with Concussion, Brain and Concussion, Mild, run by Akiva Cohen 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 6 inclusion and 7 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 3 Sep 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Number of participants that have met have met criteria for recovery at 28 days post-injury, defined as return to baseline symptom levels along with feeling > 90% back to normal. (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06829498, which also lists 1 linked publication.

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 3 Sep 2026.

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