Pediatric Traumatic Brain Injury Clinical Trial
Official title:
Overcoming Membrane Transporters to Improve CNS Drug Delivery
The overall purpose of this research study is to investigate the safety of pharmacological
therapies that may potentially improve pediatric outcomes after traumatic brain injury.
Traumatic brain injuries are the leading cause of death and disability among children and
young adults.
Hypothesis: Combinational therapy with a membrane transporter and antioxidant are safe after
TBI and can overcome barriers to the brain and synergistically improve bioavailability and
efficacy the antioxidant content of the body and CNS after TBI.
Specific Aim: Define the capacity of the combination of probenecid and NAC to safely and
synergistically preserve levels of GSH and reduce oxidative stress in children with severe
TBI. We will enroll 20 children age 2 to less than 18 years old (less than 216 months) after
severe TBI in a randomized, controlled study of administration of the combinational therapy
and test if the administration of these drugs is safe and if antioxidant reserve can be
preserved within the serum and CSF.
Probenecid (at the same dose that is used as an adjunct to antibiotic therapy) and NAC (at
the same dose that is used for acetaminophen-induced liver disease), or vehicles will be
given for 3 days. The primary outcomes of the study will be the safety of drug
administration and the CSF and serum levels anti-oxidant reserve (AOR), with the presumption
that maintaining anti-oxidant levels within the brain may prove neuroprotective. Other
secondary outcomes (CSF and serum probenecid, NAC, GSH and phenytoin concentrations) will
also be tested. Adverse events occuring during treatment with these drugs after TBI will be
monitored by a local Data Safety Monitoring Board.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment