Trial Outcomes & Findings for BCAA Supplementation for Concussion (NCT NCT01860404)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

Day 21

Results posted on

2024-05-14

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo will be administered orally twice daily for 21 days Placebo solution: The placebo solution will have similar taste, texture, consistency and appearance as the branched chain amino acid (BCAA) solution.	Branched Chain Amino Acids (7.5g BID) 7.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (15g BID) 15 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAA's will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (22.5g BID) 22.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (27g BID) 27 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.
Overall Study STARTED	8	8	9	9	8
Overall Study COMPLETED	5	4	4	3	4
Overall Study NOT COMPLETED	3	4	5	6	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo will be administered orally twice daily for 21 days Placebo solution: The placebo solution will have similar taste, texture, consistency and appearance as the branched chain amino acid (BCAA) solution.	Branched Chain Amino Acids (7.5g BID) 7.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (15g BID) 15 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAA's will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (22.5g BID) 22.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (27g BID) 27 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.
Overall Study Lost to Follow-up	3	4	1	6	4
Overall Study Withdrawal by Subject	0	0	4	0	0

Baseline Characteristics

BCAA Supplementation for Concussion

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=8 Participants Placebo will be administered orally twice daily for 21 days Placebo solution: The placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.	Branched Chain Amino Acids (7.5g BID) n=8 Participants 7.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAA's will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (15g BID) n=9 Participants 15 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAA's will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (22.5g BID) n=9 Participants 22.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAA's will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (27g BID) n=8 Participants 27 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAA's will be combined together and dissolved in a flavored solution.	Total n=42 Participants Total of all reporting groups
Age, Categorical <=18 years	6 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants	9 Participants n=4 Participants	6 Participants n=21 Participants	37 Participants n=10 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	5 Participants n=10 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Age, Continuous	16.5 years n=5 Participants	15 years n=7 Participants	16 years n=5 Participants	15 years n=4 Participants	15.5 years n=21 Participants	15.5 years n=10 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	4 Participants n=21 Participants	20 Participants n=10 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	4 Participants n=21 Participants	22 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	5 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	9 Participants n=4 Participants	7 Participants n=21 Participants	37 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=21 Participants	4 Participants n=10 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	7 Participants n=4 Participants	8 Participants n=21 Participants	36 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Region of Enrollment United States	8 participants n=5 Participants	8 participants n=7 Participants	9 participants n=5 Participants	9 participants n=4 Participants	8 participants n=21 Participants	42 participants n=10 Participants
Days from injury to enrollment	2 days n=5 Participants	2 days n=7 Participants	1 days n=5 Participants	2 days n=4 Participants	2 days n=21 Participants	2 days n=10 Participants

PRIMARY outcome

Timeframe: Day 21

Population: Not all participants completed daily neurocognitive testing batteries, therefore there is incompleteness in the Day 21 values. In total, only 13 participants completed neurocognitive testing on day 21 (compared to 28 participants who completed full follow-up)

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.

Outcome measures

Outcome measures
Measure	Placebo n=4 Participants Placebo will be administered orally twice daily for 21 days Placebo solution: The placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.	Branched Chain Amino Acids (7.5g BID) n=1 Participants 7.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (15g BID) n=2 Participants 15 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (22.5g BID) n=2 Participants 22.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (27g BID) n=4 Participants 27 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.
Reaction Time Difference Between Drug and Placebo Groups	2.44 log(milliseconds) Interval 2.41 to 2.51	2.49 log(milliseconds) Interval 2.44 to 2.55	2.52 log(milliseconds) Interval 2.48 to 2.56	2.48 log(milliseconds) Interval 2.46 to 2.57	2.48 log(milliseconds) Interval 2.42 to 2.49

SECONDARY outcome

Timeframe: Day 21

Population: Only 20 of 38 subjects completed daily symptom and activity logs though the 3 weeks of the study

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

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Placebo will be administered orally twice daily for 21 days Placebo solution: The placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.	Branched Chain Amino Acids (7.5g BID) n=4 Participants 7.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (15g BID) n=4 Participants 15 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (22.5g BID) n=3 Participants 22.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (27g BID) n=4 Participants 27 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.
Clinical Symptoms	3 units on a scale Interval 2.0 to 5.0	2 units on a scale Interval 0.5 to 3.0	0 units on a scale Interval 0.0 to 1.5	0 units on a scale Interval 0.0 to 0.0	0 units on a scale Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Day 21

Population: Only 20 of 38 subjects completed daily symptom and activity logs though the 3 weeks of the study

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

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Placebo will be administered orally twice daily for 21 days Placebo solution: The placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.	Branched Chain Amino Acids (7.5g BID) n=4 Participants 7.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (15g BID) n=4 Participants 15 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (22.5g BID) n=3 Participants 22.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (27g BID) n=4 Participants 27 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.
Return to Physical Activity Baseline	2 score on a scale Interval 1.0 to 2.0	1.5 score on a scale Interval 1.0 to 3.0	3 score on a scale Interval 1.0 to 5.0	3 score on a scale Interval 2.0 to 4.0	5 score on a scale Interval 3.5 to 5.0

SECONDARY outcome

Timeframe: Day 21

Population: Not all participants completed daily neurocognitive testing batteries, therefore there is incompleteness in the Day 21 values. In total, only 13 participants completed neurocognitive testing on day 21 (compared to 28 participants who completed full follow-up)

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

Outcome measures

Outcome measures
Measure	Placebo n=4 Participants Placebo will be administered orally twice daily for 21 days Placebo solution: The placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.	Branched Chain Amino Acids (7.5g BID) n=1 Participants 7.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (15g BID) n=2 Participants 15 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (22.5g BID) n=2 Participants 22.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (27g BID) n=4 Participants 27 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.
Neurocognitive Recovery-- Attention	2.65 log(milliseconds) Interval 2.6 to 2.71	2.60 log(milliseconds) Interval 2.55 to 2.65	2.73 log(milliseconds) Interval 2.67 to 2.8	2.74 log(milliseconds) Interval 2.62 to 2.86	2.69 log(milliseconds) Interval 2.65 to 2.77

SECONDARY outcome

Timeframe: Day 21

Population: All 38 participants, minus the 4 who withdrew following randomization, are included in the adherence measure

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

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Placebo will be administered orally twice daily for 21 days Placebo solution: The placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.	Branched Chain Amino Acids (7.5g BID) n=8 Participants 7.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (15g BID) n=5 Participants 15 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (22.5g BID) n=9 Participants 22.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (27g BID) n=8 Participants 27 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.
Compliance and Adherence to Treatment	81 Percent of total drink consumed Interval 14.3 to 87.9	64.3 Percent of total drink consumed Interval 28.4 to 91.4	54.8 Percent of total drink consumed Interval 15.0 to 55.6	23.8 Percent of total drink consumed Interval 11.9 to 42.5	49.0 Percent of total drink consumed Interval 22.7 to 72.6

SECONDARY outcome

Timeframe: Day 21

Population: Adverse events were only evaluated for the 38 subjects who participated. The 4 subjects who withdrew did so prior to receiving any study medication.

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

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Placebo will be administered orally twice daily for 21 days Placebo solution: The placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.	Branched Chain Amino Acids (7.5g BID) n=8 Participants 7.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (15g BID) n=5 Participants 15 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (22.5g BID) n=9 Participants 22.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (27g BID) n=8 Participants 27 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.
Tolerability of BCAA's Based on Adverse Events	3 Participants	3 Participants	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 21

Population: Only the 38 participants who received any study drug are included. The 4 who withdrew did so immediately after randomization before consuming any product.

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.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Placebo will be administered orally twice daily for 21 days Placebo solution: The placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.	Branched Chain Amino Acids (7.5g BID) n=8 Participants 7.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (15g BID) n=5 Participants 15 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (22.5g BID) n=9 Participants 22.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (27g BID) n=8 Participants 27 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.
Safety and BCAA Supplementation	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 21

Population: Not all participants completed daily neurocognitive testing batteries, therefore there is incompleteness in the Day 21 values. In total, only 13 participants completed neurocognitive testing on day 21 (compared to 28 participants who completed full follow-up)

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.

Outcome measures

Outcome measures
Measure	Placebo n=4 Participants Placebo will be administered orally twice daily for 21 days Placebo solution: The placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.	Branched Chain Amino Acids (7.5g BID) n=1 Participants 7.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (15g BID) n=2 Participants 15 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (22.5g BID) n=2 Participants 22.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (27g BID) n=4 Participants 27 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.
Neurocognitive Recovery-- Working Memory	2.69 log(milliseconds) Interval 2.62 to 2.78	2.70 log(milliseconds) Interval 2.59 to 2.8	2.84 log(milliseconds) Interval 2.82 to 2.87	2.82 log(milliseconds) Interval 2.68 to 2.97	2.74 log(milliseconds) Interval 2.66 to 2.91

SECONDARY outcome

Timeframe: Day 21

Population: Not all participants completed daily neurocognitive testing batteries, therefore there is incompleteness in the Day 21 values. In total, only 13 participants completed neurocognitive testing on day 21 (compared to 28 participants who completed full follow-up)

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

Outcome measures

Outcome measures
Measure	Placebo n=4 Participants Placebo will be administered orally twice daily for 21 days Placebo solution: The placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.	Branched Chain Amino Acids (7.5g BID) n=1 Participants 7.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (15g BID) n=2 Participants 15 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (22.5g BID) n=2 Participants 22.5 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.	Branched Chain Amino Acids (27g BID) n=4 Participants 27 grams of BCAAs will be administered twice-daily for 21 days Branched Chain Amino Acids: The three BCAAs will be combined together and dissolved in a flavored solution.
Neurocognitive Recovery-- Visual Memory	1.24 score on a scale Interval 1.15 to 1.29	1.11 score on a scale Interval 0.88 to 1.34	0.99 score on a scale Interval 0.93 to 1.04	0.75 score on a scale Interval 0.22 to 1.27	1.05 score on a scale Interval 0.99 to 1.08

SECONDARY outcome

Timeframe: Day 21

Population: Only 20 of 38 subjects completed daily symptom and activity logs though the 3 weeks of the study

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