Concussion (Diagnosis)Phase 2NCT07670195
BCAAs in Concussion 3.0
A Phase 2 study testing BCAA in people with Concussion (Diagnosis) and MTBI - Mild Traumatic Brain Injury, run by Akiva Cohen at 1 site in United States.
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 yearsHealthy volunteers can take part
- Conditions the study is for
- Concussion (Diagnosis), MTBI - Mild Traumatic Brain Injury, Concussion, Brain
- What is being tested?
- BCAA
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Aug 2026to Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Healthy volunteers accepted
- 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.
- One or more clinical signs or two or more acute symptoms with at least one VVE abnormality.
- Present within 4 days of injury.
- Post-menarchal females must have a negative urine pregnancy test.
- 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 TBI, including 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.
- 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. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's Hospital of Philadelphia
Havertown, Pennsylvania, 19083
Daniel Corwin, MD, 215-327-2306, corwind@chop.edu
Olivia Podolak, 862-668-7645, podolako@chop.edu
About this study
Official title: HIT HEADS 3.0: 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. This third trial was developed to inform clinical practice around BCAA treatment in concussion in a new formulation.
- Being tested
- BCAA, Placebo
- Keywords
- Concussion, mTBI, BCAAs, Branched Chain Amino Acids
- Medical subject headings
- Brain Concussion, Disease
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 into a powder formulation.
PlaceboOther
The placebo formulation will have similar taste, texture, consistency and appearance as the BCAA formulation.
| Study group | Role | What they receive |
|---|---|---|
| Drug: Branched Chain Amino Acids | Experimental | The three BCAAs will be combined together into a powder formulation. Receives: Drug: BCAA |
| Placebo | Placebo comparator | The placebo formulation will have similar taste, texture, consistency and appearance as the BCAA formulation. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Determine whether administration of high-dose BCAAs (30g/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
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
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
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
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
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
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
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
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
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
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
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
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.
- First posted26 Jun 2026
- Study start5 Aug 2026
- Primary completionJun 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Concussion (Diagnosis)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Akiva Cohen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Akiva Cohen, Children's Hospital of Philadelphia
- Investigators
- Daniel Corwin, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07670195
- Sponsor's protocol ID
- 23-024503
- Status last verified
- Aug 2026
- First submitted
- 19 Jun 2026
- 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
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HIT HEADS 3.0: Head Injury Treatment: A Randomized, Placebo-controlled, Double-blinded, Therapeutic Clinical Trial of Branched Chain Amino Acids (BCAAs) in the Treatment of Concussion
- ClinicalTrials.gov ID
- NCT07670195
- Acronym / sponsor ID
- 23-024503
- Keywords
- Concussion, mTBI, BCAAs, Branched Chain Amino Acids
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Akiva CohenUniversity, hospital or other
- Study start
- 5 Aug 2026 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 26 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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. This third trial was developed to inform clinical practice around BCAA treatment in concussion in a new formulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Drug: Branched Chain Amino Acids | Experimental | Drug: BCAAThe three BCAAs will be combined together into a powder formulation. |
| Placebo | Placebo comparator | Other: PlaceboThe placebo formulation will have similar taste, texture, consistency and appearance as the BCAA formulation. |
Who may qualify
- Ages
- 11 to 23 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (6 listed)
- Evidence of moderate or severe TBI, including 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.
- Participants who are pregnant, planning on becoming pregnant during the study duration, or breastfeeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BCAAThe three BCAAs will be combined together into a powder formulation. | Drug | Drug: Branched Chain Amino Acids |
| PlaceboThe placebo formulation will have similar taste, texture, consistency and appearance as the BCAA formulation. | Other | Placebo |
Primary outcome
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.
13 secondary outcomes
Determine whether administration of high-dose BCAAs (30g/day) compared to placebo supplementation, promotes concussion recovery operationalized by the return to baseline (pre-injury) concussion symptom levels.
Time frame: 28 days
Determine whether administration of BCAAs leads to a lower visio-vestibular abnormality burden compared to placebo.
Time frame: 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
Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities--minimum pupil diameter compared to placebo.
Time frame: 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
Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-constriction latency compared to placebo.
Time frame: 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
Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities--peak constriction velocity compared to placebo.
Time frame: 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
Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-peak dilation velocity compared to placebo.
Time frame: 28 days
Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-T75 compared to placebo.
Time frame: 28 days
Determine whether administration of BCAAs leads to subjective improvement in sleep quality compared to placebo.
Time frame: 28 days
Determine whether administration of BCAAs leads to subjective improvement in physical activity compared to placebo.
Time frame: 28 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2026.
- Background: PubMed 38468511Corwin 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Daniel Corwin, MD principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BCAA in people with Concussion (Diagnosis) and MTBI - Mild Traumatic Brain Injury, 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 7 inclusion and 6 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: looking for participants now, 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Olivia E. Podolak (8626687645, podolako@chop.edu), or a site near the patient. 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 NCT07670195, 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; AzTrials last refreshed its copy on 26 Oct 2026.