BCAAs in Concussion 2.0

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: Active, not recruiting
• Conditions: Concussion; Concussion, Mild; Concussion, Brain
• Intervention / Treatment: Drug: BCAA; Other: Placebo

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: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

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.	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

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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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

• Sponsor: Akiva Cohen
• Investigators: Principal Investigator: Daniel Corwin, MD, Children's Hospital of Philadelphia

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: January 30, 2025
• First Submitted That Met QC Criteria: February 13, 2025
• First Posted (Actual): February 17, 2025

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Injuries, Traumatic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Brain Concussion
• Other Study ID 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