The National Institute of Neurological Disorders and Stroke (NINDS) has announced two major research initiatives — one, focusing on research on stroke; the other, on studies related to concussion.
The new stroke network will comprise a consortium of 25 regional stroke centers that will work with hundreds of hospitals across the country to test potential treatments and improve outcomes for those who suffer stroke.
Studies that are funded by the network will have a single institutional review board (IRB), a centralized review and approval master contract process, and a funding infrastructure to streamline execution of clinical trials. The studies in the new NIH Stroke Trials Network — or NIH StrokeNet — will attempt a balanced focus on prevention, treatment, and recovery.
The stroke centers that are part of NIH StrokeNet will bring a wide range of specialties — emergency medicine, interventional neuroradiology, vascular neurology, neurosurgery, neuroscience nursing, neurointensive care, stroke rehabilitation, neuroimaging, and pediatric neurology — in a coordinated effort to advance stroke treatment. Each center will receive funding over a five-year period, with $200,000 in research costs and $50,000 for training stroke clinical researchers each year for the first three years. Additional funding will be provided once individual centers complete study milestones.
The University of Cincinnati will manage the national clinical coordinating center, including the development of the central IRB and trial agreements for the regional centers. A national data management center will be selected in February, said Scott Janis, PhD, program director in the Office of Clinical Research at NINDS. The network will initially take on several NIH stroke projects that have already been launched, he said, and calls for new trials will be announced later this year.
The NINDS supports two other networks, the Neurological Emergencies Treatment Trials Network (NETT) and Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT). The goal is to have a learning infrastructure in place that will become more efficient with each trial.
“We won't have to reinvent the wheel,” said Joseph P. Broderick, MD, chairman of neurology at the University of Cincinnati and director of Greater Cincinnati-Northern Kentucky Stroke Research, and director of the Neuroscience Institute. “This will make it easier to recruit patients and speed up the time it takes to design, implement, and carry out studies. We have a huge amount of work to do in stroke recovery, acute treatment, and prevention.”
Walter J. Koroshetz, MD, deputy director of the NINDS, agrees. “The NIH StrokeNet will allow the most promising therapies to quickly advance to the clinic, to improve prevention, acute treatment, or rehabilitation of the stroke patient. We need to have a balance of approaches to decrease the burden of illness due to stroke.”
A year after the National Football League committed $30 million to the Foundation for the National Institutes of Health, the NIH announced funding for the first eight projects to understand the acute and long-term effects of traumatic brain injury and repeated concussions on athletes.
Part of the problem is that there is no way to predict the longer term effects of concussion, or know which athletes are at risk for progressive brain degeneration, called chronic traumatic encephalopathy (CTE).
Six pilot projects were funded to study early stages of concussion in young athletes or animal models of concussion. Two of the studies are large multicenter cooperative agreements to characterize the scope of long-term changes following head injury. The ultimate goal of these studies is to develop ways to diagnose CTE in living people.
Currently, CTE can only be accurately diagnosed in the brain after a person has died. In the two cooperative studies, neuropathologists from eight universities will study brain tissue from individuals exposed to various TBI exposures to define the scope of brain pathology that can occur in the years after TBI. They will then image the brain tissue to determine if MRI or PET scans can identify the chronic pathology. If successful, the imaging techniques will be useful in making clinical diagnoses in living individuals.
Ann McKee, MD, a professor of neurology and pathology and co-director of the Center for the Study of Traumatic Encephalopathy at Boston University School of Medicine, will be heading up one of the research projects. Wayne Gordon, PhD, a neuropsychologist at Mount Sinai Hospital in New York, will head the other.
The Massachusetts team will work with scientists at Washington University in St. Louis and Massachusetts General Hospital to correlate the changes seen in brain tissue with advanced brain scans.
Dr. Gordon will work with colleagues at the University of Washington to identify chronic effects of mild, moderate, and severe traumatic brain injuries and CTE in the brain. Imaging teams at Massachusetts General Hospital, University of Washington, and Oregon Health Sciences University will determine if advanced imaging techniques can identify these effects.
The University of Washington scientists have been studying thousands of persons and collecting brain tissue from donors as part of an ongoing study funded by the NIH called Adult Changes in Thought. They also have detailed medical records of donors. The study scientists will be analyzing these tissues as well as medical records and specimens. They will also examine brain tissue for chronic effects of severe TBI in persons followed in the Department of Education Model systems TBI project. The group will also look for biomarkers that might be useful to diagnose chronic effects of traumatic brain injury in living patients.
Dr. Gordon said that there are about 600 brains in the University of Washington brain bank and that about 20 percent have evidence of traumatic brain injury.
Both teams will also work with NIH to design a registry of people with a history of traumatic brain injury willing to donate brain and spinal cord tissue at death. This NIH Neurobiobank will manage the collection and distribution of the specimens for research. The NIH Neurobiobank was recently launched to support research in a number of neurologic and psychiatric disorders in which brain tissue is essential to advance the science.
The six pilot grants include studies on sports concussion in school-age athletes; testing of a concussion injury management app for youth sports; study of eye movement as a window into concussion or mild traumatic brain injury; effectiveness of imaging scans and biomarkers in adolescence that might predict who is ready to return to the ball field after concussion; tests of somatosensory processing in young people following concussion and recovery; and the identification and characterization of small molecules in the brain that are formed on the heels of head injury. This last study will be conducted on mouse models of concussion.
“We need to understand the longer term effects of concussion, especially repetitive concussions,” said Dr. Koroshetz, MD, of the NINDS. “We hope to eventually predict who is at risk for developing a prolonged post-concussive syndrome and who is at risk for chronic neurodegeneration so we can treat these problems early on. It's an effort that we hope will provide important answers to athletes and their families.”