Highlights of Funded Active Research Projects
Epilepsy
Safety and Effectiveness of Open-Label Clobazam in Subjects with Lennox-Gastaut Syndrome (PI: Jeffrey Buchhalter, MD, PhD)
The Lennox-Gastaut syndrome (LGS) is a disease associated with severe seizures in childhood. The initial events usually appear during the first seven years of life. Individuals with LGS experience multiple seizure types. Clobazam is a medication that prevents the brain from initiating seizures and it is particularly effective for drop seizures, a type of epilepsy in which the body or parts of the body stiffen and fall. The “drop” can involve the entire body, trunk or head and it can subsequently lead to falls and injuries depending on the position of the subject at the time of the seizure. Individuals with LGS also present with cognitive dysfunction that progresses rapidly if the seizures are not controlled adequately. This study is being performed to assess the safety and effectiveness of clobazam for the treatment of seizures associated with LGS.
Placebo-Controlled, Escalating Dose, Multiple Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetic of Pregabalin in Pediatric Patients with Partial Onset Seizures (PI: Jeffrey Buchhalter, MD, PhD)
Epilepsy is a common childhood disorder affecting 4 to 5 out of 1,000 children. Children with epilepsy often suffer from impaired academic performance and have a higher likelihood of developing behavioral difficulties, which may persist into adulthood. Although epilepsy is often well controlled with existing antiepileptic drug (AED) therapy, more than 25% of pediatric patients have seizures that are uncontrolled by currently available agents, or have adverse effects related to AEDs that complicate their seizure control. The aim of this study is to evaluate the safety, tolerability and pharmacokinetics of pregabalin, an AED already approved for use in the US as adjunctive therapy for patients with partial onset seizures. Pregabalin is also used for the treatment of peripheral neuropathy, neuropathic pain and generalized anxiety disorder. Pregabalin has the potential of improving seizure control, it is generally well tolerated and may improve the quality of life for subjects with epilepsy. This study offers potential benefit of a new adjunctive treatment for partial onset seizures in pediatric patients.
Retrospective review of the pediatric epilepsy surgery program: evaluations, procedures and outcomes (PI: P. David Adelson, MD)
Epileptic patients who fail to achieve seizure control with two initial anticonvulsant medications have only a 10% chance of achieving seizure freedom with the addition of a third medication. Epilepsy surgery has shown an efficacy of up to 80% in seizure control and it has demonstrated improved cognitive function and general development in those undergoing it. Unfortunately it is utilized by many physicians as a last resource, only justifiable when all other interventions have failed. The last 10 years have provided us with evidence that surgery is safe and effective and that it should be offered sooner. This study was designed to provide evidence of the efficacy and safety of vagus nerve stimulation (VNS) in children and to promote it as an earlier option in the epileptic child’s treatment algorithm.
Implementation of a Research Patient Data Repository at Phoenix Children's Hospital (PI: Jeffrey Buchhalter, MD, PhD)
The Research Patient Data Registry (RPDR) is a centralized clinical data registry, or data warehouse. The RPDR gathers data from various hospital systems, stores it in one place and brings clinical information to the researcher's fingertips. The two initial goals of this study were to install the necessary hardware and software to create the RPDR, and store data from children with difficult to control seizures. The development of this type of data-capture system will eventually be a tremendous resource for every investigator working in research at Phoenix Children’s, and allow them to pursue clinical research of various diseases that will enhance the lives of our patients.
Traumatic Brain Injury
Pediatric Traumatic Brain Injury Consortium: Hypothermia
(CoolKids Trial; PI: P. David Adelson, MD)
Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in children. The health burden of TBI for children, their parents and society is substantial. Despite the frequency of TBI, its impact on the health of children and years of conducted research, no new effective treatment has shown to improve functional outcome for children with severe TBIs. The Cool Kids Trial (CKT) is part of a multinational initiative developed with the goal of expanding our understanding of TBI, and improving the outcomes of children suffering traumatic brain injuries. The CKT is a study that promotes the use of moderate hypothermia (90-91ºF) as a treatment for severe traumatic brain injury. It is designed to study the effect of hypothermia on functional outcomes after traumatic brain injury in children. Phoenix Children’s Hospital is the Coordinating Center for this international effort and oversees 38 participating clinical sites around the world. The information gained from this study will improve the care for children suffering from TBI.
Other
A Practical Brain-Computer Interface Based on Micro-ECoG Technology (PI: P. David Adelson, MD)
Arizona is the second-fastest growing state in the nation and the number of people with brain disorders is estimated to increase considerably in years to come. People with neurological conditions such as stroke, amyotrophic lateral sclerosis or spinal cord injury often lack the capacity to communicate and the motor abilities necessary to independently perform in daily activities. They are usually confined to a bed or a wheel chair and their communication is slow, difficult and often hard to follow. In this study, the Institute’s researchers, in collaboration with the researchers at Arizona State University, will provide an important step towards the future creation of a device that will provide patients with brain or spinal cord disorders a means to communicate and better interact with their environment through computers that will control/move artificial limbs or robots.
Neurodevelopmental Outcome Following Congenital Heart Surgery: Evaluation of Cooling and Antegrade Cerebral Perfusion
(PI: Janet Blackham, PhD)
As treatment and longevity of children with congenital heart disease improves, recognition of neuro-developmental disabilities greatly enhances function and ultimate success in school. Although some congenital heart lesions have been suggested to cause pre-surgical brain injury, it is well recognized in the literature that surgery itself influences neurocognitive outcome. As many as 30 to 50% of children with congenital heart disease have significant neurodevelopmental abnormalities post surgery. This study looks at children who have had cardiac surgery performed at Phoenix Children’s within the last 12 years. The purpose of this study is to evaluate the relationship between the type of brain preservation technique utilized during cardiac surgery and the child’s current neurodevelopmental status.
Phoenix Children’s Hospital Neuro NICU Research Registry
(PI: Cristina Carballo, MD)
The Neuro NICU is a subspecialty unit within the Neonatal Intensive Care Unit (NICU) and provides each neurologically affected newborn the benefits of innovative neurologic diagnosis and treatment plans. The development of the second Neuro NICU in the country at Phoenix Children’s Hospital and the first in the Southwest brings this state-of-the-art expertise in the field of Neonatal Neurology and has the potential to improve the neurodevelopmental outcome of this patient population. The NICU Research Registry, with parents’ permission, allows for collection of information about children treated in the Neuro NICU for the purpose of performing retrospective research studies to evaluate the impact of treatment on their subsequent development. This registry also helps investigators identify patients who may be eligible for participation in future research studies and is fundamental for future program improvement.
