Overcoming Membrane Transporters to Improve CNS Drug Delivery - Improving Brain Antioxidants After Traumatic Brain Injury (Pro-NAC)
Recruitment status was Recruiting
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.
Pediatric Traumatic Brain Injury
Drug: Probenecid and N-acetyl cysteine
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Overcoming Membrane Transporters to Improve CNS Drug Delivery|
- Adverse Events [ Time Frame: 14 days after drug administration ] [ Designated as safety issue: Yes ]A number of a prior defined adverse events have been defined. The number of adverse events in the treatment arms will be calculated and compared.
- Antioxidant Reserve [ Time Frame: Within 5 days of injury ] [ Designated as safety issue: No ]Antioxidant reserves in CSF and serum will be calculated in both treatment arms and compared.
|Study Start Date:||March 2011|
|Estimated Study Completion Date:||March 2014|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Probenecid and N-acetyl cysteine will be administered at standard doses for the first 4 days after TBI.
Drug: Probenecid and N-acetyl cysteine
After obtaining written parental consent, patients will be randomized by the use of a blind envelope system to one of the following: to receive probenecid (initial: 25 mg/kg/dose; maintenance: 10mg/kg/dose 4 x per day for 11 doses) and NAC (initial: 140mg/kg/dose; maintenance: 70mg/kg/dose 6 x per day for 17 doses) or the placebo via nasogastric (NG) or orogastric (OG) tube for 3 days or to receive placebos.
Placebo Comparator: Placebo
Placebos will be prepared for the two experimental drugs and administered at identical time periods.
After obtaining written parental consent, patients will be randomized by the use of a blind envelope system to one of the following: to receive probenecid (initial: 25 mg/kg/dose; maintenance: 10mg/kg/dose 4 x per day for 11 doses) and NAC (initial: 140mg/kg/dose; maintenance: 70mg/kg/dose 6 x per day for 17 doses) or the placebo via nasogastric (NG) or orogastric (OG) tube for 3 days. Placebo contents include equal volumes and dosing regimens of lactose powder (for opacity) suspended in Ora-Plus and normal saline.
Other Name: Ora Plus
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01322009
|Contact: Michael J Bell, MDfirstname.lastname@example.org|
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh of UPMC||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15213|
|Contact: Michael J Bell, MD 412-692-5164 email@example.com|
|Principal Investigator: Michael J Bell, MD|
|Principal Investigator: Robert SB Clark, MD|
|Principal Investigator:||Michael J Bell, MD||University of Pittsburgh|
|Study Director:||Robert SB Clark, MD||University of Pittsburgh|