BCAAs in Concussion 2.0

September 1, 2026 updated by: Akiva Cohen

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
17

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19146
        • Children's Hospital of Philadelphia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Drug: Branched Chain Amino Acids
The three BCAAs will be combined together and dissolved into a flavored solution.
Drug: BCAA
The three BCAAs will be combined together and dissolved in a flavored solution.
Placebo Comparator: Placebo
The placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.
Other: Placebo
The placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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.
28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 28 days
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.
28 days
Determine whether administration of BCAAs leads to a lower visio-vestibular abnormality burden compared to placebo.
Time Frame: 28 days
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.
28 days
Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities--maximum pupil diameter compared to placebo.
Time Frame: 28 days
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.
28 days
Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities--minimum pupil diameter compared to placebo.
Time Frame: 28 days
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.
28 days
Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-percentage of pupil constriction compared to placebo.
Time Frame: 28 days
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.
28 days
Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-constriction latency compared to placebo.
Time Frame: 28 days
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.
28 days
Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-average constriction velocity compared to placebo.
Time Frame: 28 days
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.
28 days
Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities--peak constriction velocity compared to placebo.
Time Frame: 28 days
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.
28 days
Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-average dilation velocity compared to placebo.
Time Frame: 28 days
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.
28 days
Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-peak dilation velocity compared to placebo.
Time Frame: 28 days
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.
28 days
Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-T75 compared to placebo.
Time Frame: 28 days
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.
28 days
Determine whether administration of BCAAs leads to subjective improvement in sleep quality compared to placebo.
Time Frame: 28 days
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.
28 days
Determine whether administration of BCAAs leads to subjective improvement in physical activity compared to placebo.
Time Frame: 28 days
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.
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Akiva Cohen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Daniel Corwin, MD, Children's Hospital of Philadelphia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2025

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 30, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 13, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 17, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 1, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 23-021206

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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