BCAA's in 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: Recruiting
• 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 (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Casy Swann; Phone Number: 267-432-2862; Email: swannc@chop.edu
• Study Contact Backup: Name: Sage Myers, MD; Phone Number: 267-426-7939; Email: myerss@chop.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • The Children's Hospital of Philadelphia
      • Contact: Sage Myers, MD; Phone Number: 267-426-7939; Email: myerss@chop.edu
      • Contact: Casey Swann; Phone Number: 267-432-2862; Email: swannc@chop.edu
      • Principal Investigator: Sage Myers, MD
      • Sub-Investigator: Akiva Cohen, PhD

Participation Criteria

Eligibility Criteria

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

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	Days 3-6, 7-10, 11-14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical symptoms	Evaluate whether BCAA supplementation reduces the time to clinical symptom resolution.	Days 3-6, 7-10, 11-14
Return to school and sports	Determine whether BCAA supplementation reduces the time to return to school or work, and participation in sports.	Days 3-6, 7-10, 11-14
Neurocognitive recovery	Determine whether administration of BCAA's reduces the time for neurocognitive recovery for the cognitive domains of attention, learning, and working memory, which are the additional subcomponents of the Axon Sports Computerized Cognitive Assessment Tool.	Days 3-6, 7-10, 11-14
Compliance and Adherence to Treatment	Adherence to treatment among dosage groups versus placebo and as a function of time.	Day 21
Tolerability of BCAA's Based on Adverse Events	Assess the tolerability of BCAA doses based on subject reported adverse events.	Day 21
Safety and BCAA Supplementation	Asses the safety of BCAA doses in concussed athletes through subject reported adverse events (AEs)and serious adverse events (SAEs).	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: January 1, 2014
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Actual): March 24, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

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