Neurological Emergencies Treatment Trials Network (NETT)
Lewis Katz School of Medicine at Temple University faculty member Dr. Nina Gentile heads the regional efforts of a nationwide Neurological Emergencies Treatment Trials Network (NETT) initiative that will lead the way in providing better treatment of patients with neurological emergencies such as traumatic brain injury, stroke and seizures.
Residents and students are invited to participate in on-going studies and to initiate related investigational studies under the guidance of Dr. Nina Gentile, Director of Research and PI, Philadelphia area Neurological Emergencies Treatment Trials network (Phila-NETT).
NETT research studies include:
- ALIAS (High Dose Albumin Therapy for Neuroprotection in Acute Ischemic Stroke)
- RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial)
- ProTECT (Progesterone for Traumatic Brain Injury: Experimental Clinical Treatment)
- POINT (Platelet Oriented Inhibition in New TIA Trial)
- ARTIC (Acute Rapid Cooling for Traumatic Injuries of the Cord)
- SHINE (Stroke Hyperglycemia Insulin Network Effort)
- Exception from Informed Consent
Principal Investigator: Myron Ginsberg, MD, University of Miami
Status: Enrolling, current NIH funding for the ALIAS Phase III Trial extends to May 2010
The purpose of the ALIAS trial is to evaluate the effectiveness of high-dose, intravenous human serum albumin. Human serum albumin is a natural protein already in clinical use for a variety of indications. In animal laboratory studies it has been shown that it reduces the size of the infarction (amount of tissue death) in the brain and improves neurological function after a stroke and also decreases or eliminates the brain swelling that may occur; these effects may reduce or prevent the brain damage resulting from a stroke in humans.
Principal Investigator: Robert Silbergleit, MD, University of Michigan
Status: Funded, enrolling
Status epilepticus, a condition of persistent seizures that do not stop, is a true neurologic emergency associated with significant death and disability. Paramedics treat status epilepticus with anti-seizure medicine, but giving medicine through a vein can be difficult or slow in a seizing patient. This study will determine (1) if the anti-seizure drug midazolam given as a shot in the muscle stops seizures as well as the anti-seizure medicine lorazepam given directly into a vein, and (2) the rapidity and safety of these two medicines given in these different ways.
The nature of neurological emergencies research, like that of resuscitation research, is such that effective therapies are likely to have therapeutic windows so short that clinical trials of these interventions cannot be accomplished with a meaningful and fully informed consent process. Many NETT studies, e.g. RAMPART, the rapid administration of medication by paramedics will be conducted using exception from informed consent.
Principal Investigator: David Wright, MD, Emory University
Status: Funded, preparing for enrollment, project enrollment to begin Spring 2010
Traumatic brain injury (TBI) is a major cause of premature death and disability worldwide. With the exception of mannitol, no therapy has been found to be effective in reducing mortality and improving functional outcomes. Progesterone is a steroid found to have powerful neuroprotective properties in multiple different animal models of brain injury. Based on encouraging pilot clinical trial results, the ProTECT trial will determine the efficacy and confirm safety of this treatment in adults with moderate to severe TBI. The RAMPART study will be conducted using special rules for studies in which the subjects are too sick or incapacitated to either agree to or decline to participate at the time they are being treated in the ambulance or in the Emergency Room. To learn more about these rules, referred to as "exception from informed consent for emergency research" click on the exception from informed consent link.
Principal Investigator: Clay Johnston, MD, University of California, San Francisco
Transient ischemic attacks (TIA) are common, with an estimated 250,000-350,000 occurring each year in the US, an incidence about 30-40% that of stroke. Rapid recovery of cerebral ischemia (reduction of blood flow to the brain) is a defining characteristic of TIA and distinguishes it from completed stroke. This recovery defines a distinct pathophysiologic feature that generally indicates the presence of previously ischemic tissue still at risk: a characteristic that may be responsible for greater instability. In fact, numerous studies have shown that short-term risk of stroke is high after TIA, particularly in the first few days, even in patients treated with aspirin, the current standard of care. Antithrombotic therapy may play a distinct role in this acute pathophysiology. Effective therapies in those with TIA could significantly reduce the overall burden of stroke if initiated immediately. However, no large-scale trial has evaluated an acute intervention in patients with TIA.
The Primary Specific Aim of this randomized, double-blind, multicenter clinical trial is to determine whether clopidogrel (Plavix) 75 mg/day by mouth after a loading dose of 600 mg is effective in reducing the 90-day risk of major ischemic vascular events (ischemic stroke, myocardial infarction, and ischemic vascular death) when initiated within 12 hours of TIA onset in patients receiving aspirin 50-325 mg/day.
Principal Investigator: Michael Wang, MD, University of Miami
Status: Submitted, pending review
Traumatic spinal cord injury affects an estimated 11,000 people in the United States each year, most commonly affecting young adults in the prime of their life. Advances in the medical management of this patient population have resulted in improvements in the survivability of these injuries, with a majority of patients having a near-normal life expectancy. Thus, because of its devastating consequences but high likelihood of long-term survivability, exerts a disproportionate medical, social and economic toll. A great deal of research has been directed at identifying interventions which may mitigate the secondary mechanisms which lead to neurological worsening and impede native recovery. However, to date there have been no clinical trials definitively demonstrating the efficacy of acute interventions to improve neurological outcomes in humans with traumatic spinal cord injuries.
The NETT has proposed a randomized, controlled, multi-center study to investigate the efficacy of modest intravascular hypothermia (33.5 + 0.2° C) for improving neurological function following both complete and incomplete spinal cord injuries in humans. Significant improvement will be determined by a greater than 10 point difference between the two treatment arms in the mean change in motor score as determined at 12 month follow-up. Additional outcome measures will include ASIA sensory scores and measures of pain and disability. It is anticipated that such a study will answer the question of whether emergent intravascular cooling, a method which has shown promise in the laboratory, can improve the neurological function and independence of patients suffering from spinal cord injuries.
Principal Investigator: Karen Johnston, MD, University of Virginia
Status: Submitted, reviewed October 2009
This is a multicenter, prospective, randomized, controlled trial, with blinded outcomes. It aims to determine the efficacy and provide further safety data on the use of insulin infusion therapy for glucose control in hyperglycemic acute ischemic stroke patients. Treatment with insulin infusion will be given within 12 hours of symptom onset. The primary outcome to be assessed at 90 days will be the difference in favorable outcome measured by the modified Rankin Scale score in the insulin infusion group compared to the control group. The rates of symptomatic hypoglycemia with prolonged neurological worsening as well as asymptomatic hypoglycemia will be assessed. The secondary outcomes will assess additional neurological and functional outcomes. This highly collaborative research program is nearly guaranteed to advance the field of stroke care.
Exception from Informed Consent
The nature of neurological emergencies research, like that of resuscitation research, is such that effective therapies are likely to have therapeutic windows so short that clinical trials of these interventions cannot be accomplished with a meaningful and fully informed consent process.
International medical ethics guidelines support the conduct of such research using an exception to the requirement for informed consent for emergency research, and since 1996 US Federal Regulations have described which trials are eligible for this exception and the additional processes to be used to safeguard subjects in these trials. We anticipate that trials requiring this exception will occur with regularity in NETT. We will be developing resources and methods that the network will need to provide to our Hubs in order to meet or surpass the appropriately rigorous requirements in the Federal 50.24Exception to Informed Consent for Emergency Research regulations such as community consultations and public notification. We are also exploring the creation of a special Emergency Research Central IRB, and will facilitate local specialized IRB training. Learn more about the exception to informed consent requirements by reading the draft FDA guidance. (PDF)
Studies such as RAMPART, Rapid Anticonconvulsant by Paramedics Prior to Arrival, and ProTECT, Progresterone in Traumatic Brain Injury will be conducted using EFIC waiver.