Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II)
Principal Investigator: Jason Wilson, MD
ATACH-II is a five (5) year, multi-center, randomized, controlled, Phase-III trial with blinded outcome ascertainment to determine the efficacy of early, intensive antihypertensive treatment using intravenous nicardipine for acute hypertension in subjects with spontaneous supratentorial ICH. The ATACH-II clinical trial is funded by the National Institute of Neurological Disorders and Stroke part of the National Institutes of Health.
The primary hypothesis of this large, streamlined, focused trial is that intensive systolic blood pressure (SBP) reduction using (IV) nicardipine with treatment initiated within three (3) hours of onset of ICH and continued for the next 24 hours reduces the likelihood of death of disability at (3) months after ICH by ten percent (10%) or greater compared with standard SBP reduction. The underlying mechanism for this expected beneficial effect of intensive treatment is presumably mediated through reduction of the rate and magnitude of hematoma expansion observed in approximately seventy-three percent (73%) of patients with acute ICH.
ATACH-II will recruit a maximum of 1,280 subjects with ICH who meet the eligibility criteria. The trial will have important public health implications as it will provide necessary information regarding the efficacy and safety of antihypertensive treatment of acute hypertension in subjects with ICH. BP treatment represents a strategy that can be made widely available without the need of specialized equipment and personnel, and therefore can make a major impact upon outcome in patients with ICH. NCT01176565
Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-Protect)
Principal Investigator: Jason Wilson, MD
CSM (Cervical spondylotic myelopathy) is the most common cause of spinal cord injury worldwide. While there is evidence from the recently completed SpineNet prospective study that surgical decompression is an effective treatment for CSM, it is clear that many patients have remaining neurological impairment. While surgery is relatively safe, approximately 3% of patients maintain a neurological problem. Given this background and data from preclinical models of non-traumatic and traumatic spinal cord injury, there is strong evidence to consider the potential benefit of adding a neuroprotective drug which aids in the treatment of patients with CSM whom are undergoing surgical decompression. Riluzole is FDA-approved for the treatment of amyotrophic lateral sclerosis (ALS), which has some similar clinical feautres to CSM. Riluzole is currently under investigation for traumatic spinal cord injury. Given this background, there is a strong basis to consider studying the potential neurological benefits of Riluzole as a treatment to surgical decompression in patients with CSM. NCT01257828
Genetic Regulatory Mechanisms in Growth and Invasiveness of Glioblastoma Multiforme (GBM)
Principal investigators: Walter J. Lukiw, MS, PhD and Frank Culicchia, MD
This study examines basic gene expression and regulatory mechanisms in glioblastoma multiforme (GBM), samples of which will be obtained from approximately 25 surgical specimens. Global gene expression profiles employing DNA arrays will be obtained that quantify the expression level for every single human gene (N=33,000) using HG-U133 plus 2.0 GeneChips and the Affymetrix analytical system. Altered gene expression levels will be independently verified using Northern blot analysis, RT-PCR analysis and/or Western immunoassay, and GBM morphometry will be analyzed using phase contrast microscopy and neuronal/glial specific staining. The promoters of up regulated genes will be further analyzed for transcription-factor DNA binding sites and promoter maps for mis-regulated gene families will be created. This integrated genomic-proteomic-morphometric approach will further understanding of the basic molecular mechanisms involved in GBM, and will lead to the discovery of novel therapeutic strategies and targets in the clinical treatment of GBM.