The pharmacologic management of acute spinal cord injury in humans remains equivocal despite decades of animal and clinical investigation. The National Acute Spinal Cord Injury Study (NASCIS) was established in 1977 to evaluate new treatment modalities using a multi-center randomized clinical trial (RCT) methodology. The first RCT (NASCIS I) was successfully completed in 1983. This application is for the continuation of NASCIS II, a randomized clinical trial which is testing the efficacy and safety of a high dose Methylprednisolone (30mg/K bolus and 5.4 mg/K/hr maintenance dose for 23 hours) or Naloxone (5.4 mg/K bolus and 4.0 mg/K/hr maintenance dose for 23 hours) regimen compared with placebo. Ten acute spinal cord injury studies are participating in the trial which requires 480 patients to document clinically significant changes in neurologic function. The monthly accrual of patients has averaged 11.2 rather than the predicted 13.5 and a further two years of study is required to complete patient intake into the study and complete all the one year follow-up neurological examinations. Patients must have been injured within 12 hours of admission to the Center to be eligible for the study. The 12 hour criterion, which relates the RCT to the experimental literature, was previously planned to be 18 hours and accounts for some reduction in patient accrual. Using standard protocols and procedures, neurological examinations are performed on patients in the ER, at 24, 48 and 72 hours after injury, as well as at six weeks, six months and one year after injury. The principal outcome measures are documented changes in motor function, and in pinprick touch and deep pain sensation. The study is continuously monitored for unusually high complication and mortality rates and intermittently analyzed for greater than anticipated treatment effects. NASCIS is the only established RCT network for the clinical evaluation of treatment maneuvers for acute spinal cord injury. A lack of treatment effect from the two drug regimens currently being studied would prevent costly and unnecessary treatment of patients and would directly influence much of the experimental work conducted or being planned in this area. The demonstration of a beneficial effect from either of the two drug protocols would profoundly influence the treatment of acute spinal cord injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS015078-11S1
Application #
3395953
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Project Start
1979-02-01
Project End
1991-07-31
Budget Start
1990-09-12
Budget End
1991-07-31
Support Year
11
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Bracken, M B (2001) Methylprednisolone and acute spinal cord injury: an update of the randomized evidence. Spine (Phila Pa 1976) 26:S47-54
Bracken, M B (2000) Methylprednisolone and spinal cord injury. J Neurosurg 93:175-9
Shepard, M J; Bracken, M B (1999) Magnetic resonance imaging and neurological recovery in acute spinal cord injury: observations from the National Acute Spinal Cord Injury Study 3. Spinal Cord 37:833-7
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Shepard, M J; Saftlas, A F; Leo-Summers, L et al. (1998) Maternal anthropometric factors and risk of primary cesarean delivery. Am J Public Health 88:1534-8
Bracken, M B; Shepard, M J; Holford, T R et al. (1997) Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury JAMA 277:1597-604
Zhang, H; Bracken, M B (1996) Tree-based, two-stage risk factor analysis for spontaneous abortion. Am J Epidemiol 144:989-96
Shepard, M J; Bracken, M B (1994) The effect of methylprednisolone, naloxone, and spinal cord trauma on four liver enzymes: observations from NASCIS 2. National Acute Spinal Cord Injury Study. Paraplegia 32:236-45
Duh, M S; Shepard, M J; Wilberger, J E et al. (1994) The effectiveness of surgery on the treatment of acute spinal cord injury and its relation to pharmacological treatment. Neurosurgery 35:240-8;discussion 248-9

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