BCAA Supplementation for Concussion (HIT_HEADS)

Head Injury Treatment With Healthy and Advanced Dietary Supplements (HIT HEADS): A Randomized, Placebo-controlled, Double-blinded, Therapeutic Exploratory Clinical Trial of Branched Chain Amino Acids (BCAA's) in the Treatment of Concussion

This study is a randomized, placebo-controlled, double-blinded, therapeutic exploratory clinical trial of branched chain amino acids (BCAA's) in the treatment of concussion. The aim of the study is to determine whether, compared to placebo treatment, administration of BCAA's, at one or more doses, after a concussion improves neurocognitive recovery at one or more time-periods post concussion.

Study Overview

• Status: Completed
• Conditions: Brain Concussion
• Intervention / Treatment: Drug: Placebo solution; Drug: Branched Chain Amino Acids

Detailed Description

Annually, between 100,000 to 140,000 children present to the emergency department for concussion in the United States.1 The Centers for Disease Control now estimates that 1.6 - 3.8 million sports related concussions occur each year in the United States. A large proportion of these patients have enduring cognitive and neurobehavioral problems. Concussion is a heterogeneous insult to the brain that precipitates a complex pathophysiological process that can result in a cascade of deleterious side effects. At present, there are no proven therapies to mitigate or prevent the neurocognitive and neurobehavioral consequences of concussions. The limbic hippocampus, a brain structure crucial for learning and memory, is often damaged in concussion. In preclinical studies in our laboratory, analysis of ipsilateral hippocampi isolated from mice after traumatic brain injury (TBI) demonstrated that only the concentrations of the three BCAA's (valine, isoleucine, and leucine) were significantly altered (reduced) after injury. When these brain-injured animals received dietary supplementation with BCAA's, 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. In light of these results and the increasing awareness and morbidity associated with concussion, we are proposing a pilot therapeutic exploratory clinical trial to determine the effects of BCAA's in reducing the neurocognitive side effects of concussion injury.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years to 34 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Males and females, ages 11 - 34 years, of any race.
2. Subjects who had a concussion, as diagnosed by a qualified physician, within 72 hours prior to enrollment.
3. Ability to have daily email and internet access.
4. Females must have a negative urine pregnancy test and must use an acceptable method of contraception.
5. Subjects must, in the opinion of the referring physician, have the capacity to provide informed consent.
6. Informed consent by the subject, or for subjects <18 years old both informed consent by a parent/guardian and child assent.

Exclusion Criteria

1. Witnessed seizure at the time of injury or penetrating head injury.
2. Prior concussion or TBI within 90 days.
3. Concussion or TBI severe enough to require admission to an intensive care unit for observation or intervention.
4. Previous history of TBI or concussion requiring admission to the hospital, disabling stroke, epilepsy, brain tumor, neurodegenerative condition, or psychiatric disease.
5. Subjects taking neurological or psychoactive medications as a regular daily prescription medication.
6. Known history of maple syrup urine disease or known family history of maple syrup urine disease.
7. Any investigational drug use within 30 days prior to enrollment.
8. Allergy to Food, Drug, and Cosmetic (FD&C) Red #40 (red dye 40) or Sucralose.
9. Lactating females.
10. Parents/guardians or subjects who, in the opinion of the investigators, may be non-compliant with study schedules or procedures.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo will be administered orally twice daily for 21 days	Drug: Placebo solution; The placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.
Experimental: Branched Chain Amino Acids (27g BID); 27 grams of BCAA's will be administered twice-daily for 21 days	Drug: Branched Chain Amino Acids; The three BCAA's will be combined together and dissolved in a flavored solution.
Experimental: Branched Chain Amino Acids (22.5g BID); 22.5 grams of BCAA's will be administered twice-daily for 21 days	Drug: Branched Chain Amino Acids; The three BCAA's will be combined together and dissolved in a flavored solution.
Experimental: Branched Chain Amino Acids (15g BID); 15 grams of BCAA's will be administered twice-daily for 21 days	Drug: Branched Chain Amino Acids; The three BCAA's will be combined together and dissolved in a flavored solution.
Experimental: Branched Chain Amino Acids (7.5g BID); 7.5 grams of BCAA's will be administered twice-daily for 21 days	Drug: Branched Chain Amino Acids; The three BCAA's will be combined together and dissolved in a flavored solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reaction Time Difference Between Drug and Placebo Groups	Processing speed subtest of the Axon Sports Computerized Cognitive Assessment Tool. The values provided are the median of log reaction time to the processing speed subtest, where a lower score indicates a faster time and thus improved processing speed.	Day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Symptoms	Evaluate whether BCAA supplementation reduces total symptom burden on a total symptom scale of 9 concussion symptoms rated each from 0-6, minimal value 0, maximum value 54, a higher score indicates a higher symptom burden and therefore a worse outcome	Day 21
Return to Physical Activity Baseline	Determine whether BCAA supplementation more rapidly facilitates a return to physical baseline. The physical activity score is scaled on a 6 point Likert scale (0-5), where 0 represents no activity and 5 represents full activity, therefore a higher score represents a closer return to baseline activity by the end of the study period	Day 21
Neurocognitive Recovery-- Attention	Determine whether administration of BCAAs improves the median log reaction time of the attention subtest of the neurocognitive testing battery. A lower median log reaction time represents improved attention	Day 21
Compliance and Adherence to Treatment	Adherence to treatment among dosage groups, reported as the median percent drink consumed among the group across the study period, where 100% = all drink (2 doses per day x 21 days) consumed, and 0% represents no drink consumed	Day 21
Tolerability of BCAA's Based on Adverse Events	Assess the tolerability of BCAA doses based on subject reported adverse events, measured as the percent of participants in each study arm reporting adverse events	Day 21
Safety and BCAA Supplementation	Asses the safety of BCAA doses in concussed athletes through subject reported serious adverse events (SAEs). Reported as the number of participants in each arm experiencing an SAE.	Day 21
Neurocognitive Recovery-- Working Memory	Determine whether administration of BCAAs improves the the median of log reaction time of the working memory subtest of the neurocognitive testing battery. A lower median log reaction time represents improved working memory.	Day 21
Neurocognitive Recovery-- Visual Memory	Determine whether administration of BCAAs improves the accuracy score of the visual memory subtest of the neurocognitive testing battery. A higher accuracy score (scaled 0-1.5) represents improved visual memory	Day 21
Return to Baseline Cognitive Activity	Determine whether BCAA supplementation more rapidly facilitates a return to cognitive activity baseline. The cognitive activity score is scaled on a 5 point Likert scale (0-4), where 0 represents no activity and 4 represents full activity, therefore a higher score represents a closer return to baseline cognitive activity by the end of the study period	Day 21

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: University of Pennsylvania; Pennsylvania Department of Health; Main Line Health; The Dana Foundation
• Investigators: Principal Investigator: Sage Myers, MD, Children's Hospital of Philadelphia

Publications and helpful links

General Publications

• Cole JT, Mitala CM, Kundu S, Verma A, Elkind JA, Nissim I, Cohen AS. Dietary branched chain amino acids ameliorate injury-induced cognitive impairment. Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):366-71. doi: 10.1073/pnas.0910280107. Epub 2009 Dec 7. Erratum In: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2373.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): January 1, 2023
• Study Completion (Actual): January 1, 2023

Study Registration Dates

• First Submitted: May 20, 2013
• First Submitted That Met QC Criteria: May 20, 2013
• First Posted (Estimated): May 22, 2013

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Concussion; BCAA; Branched chain amino acids; HIT HEADS
• Additional Relevant MeSH Terms: 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 Injuries, Traumatic; Brain Concussion
• Other Study ID Numbers: 13-010227