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

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.

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