Brain Concussion
Conditions
Keywords
Concussion, Branched chain amino acids, BCAA, HIT HEADS
Brief summary
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.
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.
Interventions
The three BCAA's will be combined together and dissolved in a flavored solution.
DRUGPlacebo solution
The placebo solution will have similar taste, texture, consistency and appearance as the BCAA solution.
Sponsors
The Dana Foundation
Main Line Health
University of Pennsylvania
Pennsylvania Department of Health
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
11 Years to 34 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reaction Time Difference Between Drug and Placebo Groups | Day 21 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Return to Physical Activity Baseline | Day 21 | 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 |
| Neurocognitive Recovery-- Attention | Day 21 | 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 |
| Compliance and Adherence to Treatment | Day 21 | 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 |
| Tolerability of BCAA's Based on Adverse Events | Day 21 | 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 |
| Clinical Symptoms | Day 21 | 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 |
| Neurocognitive Recovery-- Working Memory | Day 21 | 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. |
| Neurocognitive Recovery-- Visual Memory | Day 21 | 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 |
| Return to Baseline Cognitive Activity | Day 21 | 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 |
| Safety and BCAA Supplementation | Day 21 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 BCAA solution. | 8 |
| 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 BCAA's will be combined together and dissolved in a flavored solution. | 8 |
| 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. | 9 |
| 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 BCAA's will be combined together and dissolved in a flavored solution. | 9 |
| Branched Chain Amino Acids (27g BID) 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. | 8 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 4 | 1 | 6 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 4 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Branched Chain Amino Acids (7.5g BID) | Branched Chain Amino Acids (15g BID) | Branched Chain Amino Acids (22.5g BID) | Branched Chain Amino Acids (27g BID) | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 6 Participants | 7 Participants | 9 Participants | 9 Participants | 6 Participants | 37 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 5 Participants |
| Age, Continuous | 16.5 years | 15 years | 16 years | 15 years | 15.5 years | 15.5 years |
| Days from injury to enrollment | 2 days | 2 days | 1 days | 2 days | 2 days | 2 days |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 8 Participants | 6 Participants | 9 Participants | 7 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 6 Participants | 8 Participants | 7 Participants | 8 Participants | 36 Participants |
| Region of Enrollment United States | 8 participants | 8 participants | 9 participants | 9 participants | 8 participants | 42 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 20 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 5 Participants | 5 Participants | 4 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 9 | 0 / 9 | 0 / 8 |
| other Total, other adverse events | 3 / 8 | 3 / 8 | 1 / 9 | 0 / 9 | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 9 | 0 / 9 | 0 / 8 |
Outcome results
Primary
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.
Time frame: 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)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Reaction Time Difference Between Drug and Placebo Groups | 2.44 log(milliseconds) |
| Branched Chain Amino Acids (7.5g BID) | Reaction Time Difference Between Drug and Placebo Groups | 2.49 log(milliseconds) |
| Branched Chain Amino Acids (15g BID) | Reaction Time Difference Between Drug and Placebo Groups | 2.52 log(milliseconds) |
| Branched Chain Amino Acids (22.5g BID) | Reaction Time Difference Between Drug and Placebo Groups | 2.48 log(milliseconds) |
| Branched Chain Amino Acids (27g BID) | Reaction Time Difference Between Drug and Placebo Groups | 2.48 log(milliseconds) |
p-value: 0.871Kruskal-Wallis
Secondary
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
Time frame: Day 21
Population: Only 20 of 38 subjects completed daily symptom and activity logs though the 3 weeks of the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Clinical Symptoms | 3 units on a scale |
| Branched Chain Amino Acids (7.5g BID) | Clinical Symptoms | 2 units on a scale |
| Branched Chain Amino Acids (15g BID) | Clinical Symptoms | 0 units on a scale |
| Branched Chain Amino Acids (22.5g BID) | Clinical Symptoms | 0 units on a scale |
| Branched Chain Amino Acids (27g BID) | Clinical Symptoms | 0 units on a scale |
p-value: 0.14Kruskal-Wallis
Secondary
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
Time frame: Day 21
Population: All 38 participants, minus the 4 who withdrew following randomization, are included in the adherence measure
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Compliance and Adherence to Treatment | 81 Percent of total drink consumed |
| Branched Chain Amino Acids (7.5g BID) | Compliance and Adherence to Treatment | 64.3 Percent of total drink consumed |
| Branched Chain Amino Acids (15g BID) | Compliance and Adherence to Treatment | 54.8 Percent of total drink consumed |
| Branched Chain Amino Acids (22.5g BID) | Compliance and Adherence to Treatment | 23.8 Percent of total drink consumed |
| Branched Chain Amino Acids (27g BID) | Compliance and Adherence to Treatment | 49.0 Percent of total drink consumed |
p-value: 0.581Kruskal-Wallis
Secondary
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
Time frame: 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)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Neurocognitive Recovery-- Attention | 2.65 log(milliseconds) |
| Branched Chain Amino Acids (7.5g BID) | Neurocognitive Recovery-- Attention | 2.60 log(milliseconds) |
| Branched Chain Amino Acids (15g BID) | Neurocognitive Recovery-- Attention | 2.73 log(milliseconds) |
| Branched Chain Amino Acids (22.5g BID) | Neurocognitive Recovery-- Attention | 2.74 log(milliseconds) |
| Branched Chain Amino Acids (27g BID) | Neurocognitive Recovery-- Attention | 2.69 log(milliseconds) |
p-value: 0.476Kruskal-Wallis
Secondary
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
Time frame: 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)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Neurocognitive Recovery-- Visual Memory | 1.24 score on a scale |
| Branched Chain Amino Acids (7.5g BID) | Neurocognitive Recovery-- Visual Memory | 1.11 score on a scale |
| Branched Chain Amino Acids (15g BID) | Neurocognitive Recovery-- Visual Memory | 0.99 score on a scale |
| Branched Chain Amino Acids (22.5g BID) | Neurocognitive Recovery-- Visual Memory | 0.75 score on a scale |
| Branched Chain Amino Acids (27g BID) | Neurocognitive Recovery-- Visual Memory | 1.05 score on a scale |
p-value: 0.393Kruskal-Wallis
Secondary
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.
Time frame: 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)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Neurocognitive Recovery-- Working Memory | 2.69 log(milliseconds) |
| Branched Chain Amino Acids (7.5g BID) | Neurocognitive Recovery-- Working Memory | 2.70 log(milliseconds) |
| Branched Chain Amino Acids (15g BID) | Neurocognitive Recovery-- Working Memory | 2.84 log(milliseconds) |
| Branched Chain Amino Acids (22.5g BID) | Neurocognitive Recovery-- Working Memory | 2.82 log(milliseconds) |
| Branched Chain Amino Acids (27g BID) | Neurocognitive Recovery-- Working Memory | 2.74 log(milliseconds) |
p-value: 0.482Kruskal-Wallis
Secondary
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
Time frame: Day 21
Population: Only 20 of 38 subjects completed daily symptom and activity logs though the 3 weeks of the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Return to Baseline Cognitive Activity | 2 score on a scale |
| Branched Chain Amino Acids (7.5g BID) | Return to Baseline Cognitive Activity | 3 score on a scale |
| Branched Chain Amino Acids (15g BID) | Return to Baseline Cognitive Activity | 4 score on a scale |
| Branched Chain Amino Acids (22.5g BID) | Return to Baseline Cognitive Activity | 4 score on a scale |
| Branched Chain Amino Acids (27g BID) | Return to Baseline Cognitive Activity | 3 score on a scale |
p-value: 0.629Kruskal-Wallis
Secondary
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
Time frame: Day 21
Population: Only 20 of 38 subjects completed daily symptom and activity logs though the 3 weeks of the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Return to Physical Activity Baseline | 2 score on a scale |
| Branched Chain Amino Acids (7.5g BID) | Return to Physical Activity Baseline | 1.5 score on a scale |
| Branched Chain Amino Acids (15g BID) | Return to Physical Activity Baseline | 3 score on a scale |
| Branched Chain Amino Acids (22.5g BID) | Return to Physical Activity Baseline | 3 score on a scale |
| Branched Chain Amino Acids (27g BID) | Return to Physical Activity Baseline | 5 score on a scale |
p-value: 0.267Kruskal-Wallis
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Safety and BCAA Supplementation | 0 Participants |
| Branched Chain Amino Acids (7.5g BID) | Safety and BCAA Supplementation | 0 Participants |
| Branched Chain Amino Acids (15g BID) | Safety and BCAA Supplementation | 0 Participants |
| Branched Chain Amino Acids (22.5g BID) | Safety and BCAA Supplementation | 0 Participants |
| Branched Chain Amino Acids (27g BID) | Safety and BCAA Supplementation | 0 Participants |
p-value: 1Fisher Exact
Secondary
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
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Tolerability of BCAA's Based on Adverse Events | 3 Participants |
| Branched Chain Amino Acids (7.5g BID) | Tolerability of BCAA's Based on Adverse Events | 3 Participants |
| Branched Chain Amino Acids (15g BID) | Tolerability of BCAA's Based on Adverse Events | 1 Participants |
| Branched Chain Amino Acids (22.5g BID) | Tolerability of BCAA's Based on Adverse Events | 0 Participants |
| Branched Chain Amino Acids (27g BID) | Tolerability of BCAA's Based on Adverse Events | 1 Participants |
p-value: 0.203Fisher Exact
Post Hoc
Physical Activity Score Change
Change in physical activity score for increase of total study dose of 500 g in adjusted regression. This represents a change in the physical activity score for, on average, each increase of 500 g of study drug consumed between baseline and end of study period (between baseline, day 0, and day 21). The physical activity scale is 0-5, with a maximum score of 5 representing full baseline physical activity. The least squares mean for the model for each 500 g of drug consumed, with the standard error, are presented, as is the p-value for the slope parameter of the regression.
Time frame: Baseline and 21 days
Population: 26 out of 38 participants completed at least 7 measurements of the daily symptom and activity questionnaire to contribute to the overall regression analysis. Participants across all treatment arms were combined for this regression as it was, rather than in intention-to-treat analysis, a dose response analysis testing the effect of actual study drug consumed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Physical Activity Score Change | 0.503 score on a scale | Standard Error 0.164 |
p-value: 0.0053Regression, Linear
Post Hoc
Regression Model Attention Change
Change in log reaction time of the neurocognitive testing attention score for increase of total study dose of 500 g in adjusted regression. This represents a change in the log reaction time for, on average, each increase of 500 g of study drug consumed between baseline and end of study period (between baseline, day 0, and day 21). A lower reaction time (on a scale of 2.35 to 2.80) indicates faster speed and thus improved neurocognitive function. The least squares mean for the model for each 500 g of drug consumed, with the standard error, are presented, as is the p-value for the slope parameter of the regression.
Time frame: Baseline and 21 days
Population: 18 out of 38 participants completed at least 7 measurements of neurocognitive testing to contribute to the overall regression analysis. Participants across all treatment arms were combined for this regression as it was, rather than in intention-to-treat analysis, a dose response analysis testing the effect of actual study drug consumed
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Regression Model Attention Change | 0.014 log(milliseconds) | Standard Error 0.012 |
p-value: 0.2554Regression, Linear
Post Hoc
Regression Model Cognitive Activity Score Change
Change in cognitive activity score for increase of total study dose of 500 g in adjusted regression. This represents a change in the cognitive activity score for, on average, each increase of 500 g of study drug consumed between baseline and end of study period (between baseline, day 0, and day 21). The cognitive activity scale is 0-4, with a maximum score of 4 representing full cognitive baseline activity. The least squares mean for the model for each 500 g of drug consumed, with the standard error, are presented, as is the p-value for the slope parameter of the regression.
Time frame: Baseline and 21 days
Population: 26 out of 38 participants completed at least 7 measurements of the daily symptom and activity questionnaire to contribute to the overall regression analysis. Participants across all treatment arms were combined for this regression as it was, rather than in intention-to-treat analysis, a dose response analysis testing the effect of actual study drug consumed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Regression Model Cognitive Activity Score Change | 0.051 score on a scale | Standard Error 0.224 |
p-value: 0.8234Regression, Linear
Post Hoc
Regression Model Processing Speed Change
Change in log reaction time of the neurocognitive testing processing speed score for increase of total study dose of 500 g in adjusted regression. This represents a change in the log reaction time for, on average, each increase of 500 g of study drug consumed between baseline and end of study period (between baseline, day 0, and day 21). A lower reaction time (on a scale of 2.35 to 2.80) indicates faster speed and thus improved neurocognitive function. The least squares mean for the model for each 500 g of drug consumed, with the standard error, are presented, as is the p-value for the slope parameter of the regression.
Time frame: Baseline and 21 days
Population: 18 out of 38 participants completed at least 7 measurements of neurocognitive testing to contribute to the overall regression analysis. Participants across all treatment arms were combined for this regression as it was, rather than in intention-to-treat analysis, a dose response analysis testing the effect of actual study drug consumed
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Regression Model Processing Speed Change | 0.008 log(milliseconds) | Standard Error 0.016 |
p-value: 0.624Regression, Linear
Post Hoc
Regression Model Working Memory Change
Change in log reaction time of the neurocognitive testing working memory score for increase of total study dose of 500 g in adjusted regression. This represents a change in the log reaction time for, on average, each increase of 500 g of study drug consumed between baseline and end of study period (between baseline, day 0, and day 21). A lower reaction time (on a scale of 2.35 to 2.80) indicates faster speed and thus improved neurocognitive function. The least squares mean for the model for each 500 g of drug consumed, with the standard error, are presented, as is the p-value for the slope parameter of the regression.
Time frame: Baseline and 21 days
Population: contribute to the overall regression analysis. Participants across all treatment arms were combined for this regression as it was, rather than in intention-to-treat analysis, a dose response analysis testing the effect of actual study drug consumed
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Regression Model Working Memory Change | 0.004 log(milliseconds) | Standard Error 0.0016 |
p-value: 0.7964Regression, Linear
Post Hoc
Regression Mode Visual Learning Change
Change in accuracy score of the neurocognitive testing processing speed score for increase of total study dose of 500 g in adjusted regression. This represents a change in the accuracy score for, on average, each increase of 500 g of study drug consumed between baseline and end of study period (between baseline, day 0, and day 21). The accuracy scale score is scaled from 0 to 1.5, and a higher score indicates higher accuracy and thus higher neurocognitive function. The least squares mean for the model for each 500 g of drug consumed, with the standard error, are presented, as is the p-value for the slope parameter of the regression.
Time frame: Baseline and 21 days
Population: contribute to the overall regression analysis. Participants across all treatment arms were combined for this regression as it was, rather than in intention-to-treat analysis, a dose response analysis testing the effect of actual study drug consumed
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Regression Mode Visual Learning Change | -0.013 score on a scale | Standard Error 0.046 |
p-value: 0.7749Regression, Linear
Post Hoc
Total Symptom Score Change
Change in total symptom score for increase of total study dose of 500 g in adjusted regression. This represents a change in the total symptom score for, on average, each increase of 500 g of study drug consumed between baseline and end of study period (between baseline, day 0, and day 21). The symptom score is scaled from 0-54, with a higher number representing a higher symptom burden and thus a worse outcome. The least squares mean for the model for each 500 g of drug consumed, with the standard error, are presented, as is the p-value for the slope parameter of the regression.
Time frame: Baseline and 21 days
Population: 26 out of 38 participants completed at least 7 measurements of the daily symptom and activity questionnaire to contribute to the overall regression analysis. Participants across all treatment arms were combined for this regression as it was, rather than in intention-to-treat analysis, a dose response analysis testing the effect of actual study drug consumed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Symptom Score Change | -4.4 score on a scale | Standard Error 1.4 |
p-value: 0.0036Regression, Linear