Clinical trial NCT06829498: BCAAs in Concussion 2.0
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Concussion, Brain
Concussion, Mild
Concussion
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
First posted: 2025-02-17
Enrollment: 150
Sex: ALL
Minimum age (years): 11
Maximum age (years): 23
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
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.
timeFrame: 28 days
Secondary outcomes:
measure: 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.
timeFrame: 28 days
measure: Determine whether administration of BCAAs leads to a lower visio-vestibular abnormality burden compared to placebo.
timeFrame: 28 days
measure: Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities--maximum pupil diameter compared to placebo.
timeFrame: 28 days
measure: Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities--minimum pupil diameter compared to placebo.
timeFrame: 28 days
measure: Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-percentage of pupil constriction compared to placebo.
timeFrame: 28 days
measure: Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-constriction latency compared to placebo.
timeFrame: 28 days
measure: Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-average constriction velocity compared to placebo.
timeFrame: 28 days
measure: Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities--peak constriction velocity compared to placebo.
timeFrame: 28 days
measure: Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-average dilation velocity compared to placebo.
timeFrame: 28 days
measure: Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-peak dilation velocity compared to placebo.
timeFrame: 28 days
measure: Determine whether administration of BCAAs leads to improved pupillary light reflex (PLR) abnormalities-T75 compared to placebo.
timeFrame: 28 days
measure: Determine whether administration of BCAAs leads to subjective improvement in sleep quality compared to placebo.
timeFrame: 28 days
measure: Determine whether administration of BCAAs leads to subjective improvement in physical activity compared to placebo.
timeFrame: 28 days
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Daniel Corwin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.