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

• To determine the number of adverse events that may be associated with the use of resveratrol in this population. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  To determine safety, Liver Function Tests will be conducted at day 7 and 30 in the boxers after experiencing a concussion to screen for asymptomatic adverse events.
  
  

• Cognitive Outcomes [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  The ImPACT cognitive test performance of each subject will be compared to their baseline scores. We hypothesize that resveratrol will improve cognitive performance after injury.
  
  
• Axonal Injury [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  We will determine the efficacy of resveratrol on decreasing axonal injury in the brain using magnetic resonance imaging (MRI) at day 7 after injury.
  
  

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.