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Use of Resveratrol to Decrease Acute Secondary Brain Injury Following Sports-Related Concussions in Boxers

Use of Resveratrol to Decrease Secondary Brain Injury Following Sports-Related Concussions: a Double-Blind, Placebo-Controlled Study

Status
Completed
Phases
Phase 1Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01321151
Acronym
REPAIR
Enrollment
12
Registered
2011-03-23
Start date
2011-03-31
Completion date
2011-11-30
Last updated
2021-02-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Sports Concussion

Keywords

Mild Brain Injury, Concussions, Resveratrol, Boxers, ImPACT, MRI

Brief summary

Sports-related concussions are a serious problem in football, boxing, and other full contact sports. After experiencing consecutive concussions, there is an increase in neurological deficits that can lead to long-term cognitive problems (Dementia pugilistica). To combat this increase in brain damage, novel strategies need to be developed to protect athletes that are participating in these full contact sports. The purpose of this study is to elucidate whether resveratrol decreases brain injury and improves brain function after experiencing a concussion in boxers.

Detailed description

Each year, approximately 3 million sports-related concussions occur in athletes. Only about 5% of these concussions are treated in the hospital setting. To date, there are no effective interventions used at decreasing the levels of oxidant injury and inflammation within these athletes. The standard form of care in these athletes is usually rest and light exercise for 1 -2 weeks, before returning to the sport. Within this brain injury population, administration of a neuro-protectant agent immediately following the concussion may alleviate or prevent secondary injury and subsequent development of long-term cognitive deficits such as Chronic Traumatic Encephalopathy (CTE) and Dementia pugilistica (DP). Since sports-related concussions are a serious problem in our youth, by using safe interventions, we believe that the levels of oxidant injury and brain inflammation will be decreased. In addition, these neuro-protective agents may improve cognition in these boxers, and decrease the incidence of DP. Following brain injury, the secondary injury that immediately follows consists of heightened damage by oxygen radicals, which in turn damages vital lipids, proteins, and nucleic acids. This damage is exacerbated by highly acidic conditions with lead to the release of iron and the production of more harmful oxygen radicals. An increase in these oxygen radicals has been observed from minutes to hours within the primary injury. In addition, there is an increase in inflammation as well as excitotoxicity in the brain after traumatic injury. To combat this secondary injury, the use of anti-oxidants in individuals is warranted to decrease the amount of brain damage and cognitive decline after experiencing a severe brain injury. For example, resveratrol (3,5,4'-trihydroxystilbene) which is a polyphenol compound that is commonly found in grapes, is a nutritional supplement with anti-oxidant and anti-inflammatory properties with great promise for treating TBI secondary injury. A number of researchers have demonstrated that resveratrol protect multiple organs (heart, kidney, brain) from ischemia after injury. With respect to the brain, resveratrol has been shown to protect from oxidative stress, Huntington's disease, and stroke. Additionally, following TBI in various animal models, resveratrol protected from severe brain injuries. Results from these brain studies suggest that resveratrol protects from a plethora of injuries and may afford protection from secondary injury in individuals suffering from a severe brain injury. In this pilot clinical trial, boxers (n=30) will be consented to participate in this study prior to engaging in a boxing match. The concussion history will be collected before enrolling. Baseline cognitive testing and magnetic resonance imaging (MRI) scan will be performed to obtain both structural and functional data. Only 12 boxers that have a concussion will be enrolled in this study. After participating in the boxing match, if the boxer has been diagnosed with having a concussion by the ringside physician, the boxers will be treated with an oral dose of the active trans-resveratrol (500 mg) or placebo within 2 hours of completion of the boxing match. The boxer will be treated with either resveratrol or placebo (depending on the randomization schedule) once a day for 30 days. Cognitive testing and MRI scans will be conducted on day 7 after the concussion.

Interventions

DRUGResveratrol

The dose of resveratrol is 500 mg. The route of administration is oral, once-a-day for 30 days after injury.

DRUGPlacebo

The placebo is a sugar pill. The route of administration is oral, once-a-day for 30 days after injury.

Sponsors

University of Texas Southwestern Medical Center
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes

Inclusion criteria

1. Boxers between the ages 18-35 years old 2. Both men and women 3. Boxers with an estimated concussion (Mild and Moderate) as estimated by the on-site physician or athletic trainer 4. Subject has provided full written informed consent prior to the performance of any protocol-specified procedure

Exclusion criteria

1. Immediate hospitalization for sports-related concussion (Severe Concussion) 2. Known inclusion in an interventional clinical trial 3. Patients with metal implants that would interfere with the MRI scan 4. Known anemia 5. Known Pregnancy 6. Known history of alcohol/drug abuse

Design outcomes

Primary

MeasureTime frameDescription
Liver Function Testing (Aspartate Transaminase [AST]/Alanine Transaminase [ALT] Ratios) to Screen for Adverse Events.Day 7 post concussionLiver Function Tests will be conducted on day 7 after concussion.

Secondary

MeasureTime frameDescription
Functional Connectivity in Concussed Boxers30 DaysFunctional connectivity magnetic resonance imaging
Reaction Time Composite as Assessed by Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) Cognitive Test Performance7 days post concussionThe reaction time composite score (range 0.5-0.8) is an average of: modules 3,4, 5, then divided by 3.The higher the composite score, the worse the outcomes. 1. Average correct reaction time of interference stage of module 3 (X's and O'S) - Measures the number of correctly identified items (total possible correct =12), scoring 0-12. There is 4 trials of this module completed. Measures the average reaction time for correct responses on the interference (distracter) test 2. Average correct reaction time of module 4 (Symbol Match) - Provides the number of correct matches out of 27 when the symbol number pairings are visible. The quicker the response time for each correctly identified symbol match indicates a better outcome. 3. Average correct reaction time of module 5 (Color Match) - is number of correct color matches. The quicker the response time to a correct color match is a better outcome. Each modules is measured in percentage correct

Countries

United States

Participant flow

Participants by arm

ArmCount
Sugar Pill
Placebo control Placebo: The placebo is a sugar pill. The route of administration is oral, once-a-day for 30 days after injury.
6
Resveratrol
Intervention Resveratrol: The dose of resveratrol is 500 mg. The route of administration is oral, once-a-day for 30 days after injury.
6
Total12

Baseline characteristics

CharacteristicResveratrolTotalSugar Pill
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
6 Participants12 Participants6 Participants
Age, Continuous27 years
STANDARD_DEVIATION 5.3
26 years
STANDARD_DEVIATION 5.15
26 years
STANDARD_DEVIATION 5
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
4 Participants9 Participants5 Participants
Race (NIH/OMB)
More than one race
0 Participants1 Participants1 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
2 Participants2 Participants0 Participants
Region of Enrollment
United States
6 participants12 participants6 participants
Sex: Female, Male
Female
1 Participants1 Participants0 Participants
Sex: Female, Male
Male
5 Participants11 Participants6 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 60 / 6
other
Total, other adverse events
0 / 60 / 6
serious
Total, serious adverse events
0 / 60 / 6

Outcome results

Primary

Liver Function Testing (Aspartate Transaminase [AST]/Alanine Transaminase [ALT] Ratios) to Screen for Adverse Events.

Liver Function Tests will be conducted on day 7 after concussion.

Time frame: Day 7 post concussion

Population: This Outcome measure differs from Outcome measure 1 based on the time frame. In Outcome measure 1, the time frame listed is -'30 Days post concussion' whereas within Outcome measure 2, the time frame listed is -'Day 7 post concussion'.

ArmMeasureValue (MEAN)Dispersion
Sugar PillLiver Function Testing (Aspartate Transaminase [AST]/Alanine Transaminase [ALT] Ratios) to Screen for Adverse Events.1.57 AST/ALT ratioStandard Deviation 0.4
ResveratrolLiver Function Testing (Aspartate Transaminase [AST]/Alanine Transaminase [ALT] Ratios) to Screen for Adverse Events.1.24 AST/ALT ratioStandard Deviation 0.3
Primary

Liver Function Testing (Aspartate Transaminase [AST]/Alanine Transaminase [ALT] Ratios) to Screen for Adverse Events.

Liver Function Tests will be conducted on day 30 after concussion.

Time frame: 30 Days post concussion

Population: No data was collected for30 days post concussion

Secondary

Functional Connectivity in Concussed Boxers

Functional connectivity magnetic resonance imaging

Time frame: 30 Days

Population: No data was collected for 30 days post concussion

Secondary

Reaction Time Composite as Assessed by Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) Cognitive Test Performance

The reaction time composite score (range 0.5-0.8) is an average of: modules 3,4, 5, then divided by 3.The higher the composite score, the worse the outcomes. 1. Average correct reaction time of interference stage of module 3 (X's and O'S) - Measures the number of correctly identified items (total possible correct =12), scoring 0-12. There is 4 trials of this module completed. Measures the average reaction time for correct responses on the interference (distracter) test 2. Average correct reaction time of module 4 (Symbol Match) - Provides the number of correct matches out of 27 when the symbol number pairings are visible. The quicker the response time for each correctly identified symbol match indicates a better outcome. 3. Average correct reaction time of module 5 (Color Match) - is number of correct color matches. The quicker the response time to a correct color match is a better outcome. Each modules is measured in percentage correct

Time frame: 7 days post concussion

ArmMeasureValue (MEAN)Dispersion
Sugar PillReaction Time Composite as Assessed by Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) Cognitive Test Performance.675 Composite ScoreStandard Deviation 0.103
ResveratrolReaction Time Composite as Assessed by Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) Cognitive Test Performance.695 Composite ScoreStandard Deviation 0.179
Secondary

Reaction Time Composite as Assessed by Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) Cognitive Test Performance

The reaction time composite score (range 0.5-0.8) is an average of: modules 3,4, 5, then divided by 3.The higher the composite score, the worse the outcomes. 1. Average correct reaction time of interference stage of module 3 (X's and O'S) - Measures the number of correctly identified items (total possible correct =12), scoring 0-12. There is 4 trials of this module completed. Measures the average reaction time for correct responses on the interference (distracter) test 2. Average correct reaction time of module 4 (Symbol Match) - Provides the number of correct matches out of 27 when the symbol number pairings are visible. The quicker the response time for each correctly identified symbol match indicates a better outcome. 3. Average correct reaction time of module 5 (Color Match) - is number of correct color matches. The quicker the response time to a correct color match is a better outcome. Each modules is measured in percentage correct

Time frame: 24-72 hours post concussion

Population: No data was collected for 24-72 hours post concussion

Secondary

Reaction Time Composite as Assessed by Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) Cognitive Test Performance

The reaction time composite score (range 0.5-0.8) is an average of: modules 3,4, 5, then divided by 3.The higher the composite score, the worse the outcomes. 1. Average correct reaction time of interference stage of module 3 (X's and O'S) - Measures the number of correctly identified items (total possible correct =12), scoring 0-12. There is 4 trials of this module completed. Measures the average reaction time for correct responses on the interference (distracter) test 2. Average correct reaction time of module 4 (Symbol Match) - Provides the number of correct matches out of 27 when the symbol number pairings are visible. The quicker the response time for each correctly identified symbol match indicates a better outcome. 3. Average correct reaction time of module 5 (Color Match) - is number of correct color matches. The quicker the response time to a correct color match is a better outcome. Each modules is measured in percentage correct

Time frame: 30 days post concussion

Population: No data was collected for 30 days post concussion

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026