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Overcoming Membrane Transporters to Improve CNS Drug Delivery - Improving Brain Antioxidants After Traumatic Brain Injury (Pro-NAC)

This study has been completed.
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Robert Clark, MD, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01322009
First received: March 22, 2011
Last updated: July 1, 2016
Last verified: July 2016
Results First Received: May 19, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Pediatric Traumatic Brain Injury
Interventions: Drug: Probenecid and N-acetyl cysteine
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Children 2-18 years-of-age after severe TBI (Glasgow Coma Scale [GCS] score ≤8) recruited from November 2011-September 2013 at a single, tertiary Children’s Hospital.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Drug

Probenecid and N-acetyl cysteine will be administered at standard doses for the first 4 days after TBI.

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

Placebos will be prepared for the two experimental drugs and administered at identical time periods.

Placebo: 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.


Participant Flow:   Overall Study
    Drug     Placebo  
STARTED     7     7  
COMPLETED     7     4  
NOT COMPLETED     0     3  
Death                 0                 1  
Adverse Event                 0                 1  
ng tube discontinued                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Drug

Probenecid and N-acetyl cysteine will be administered at standard doses for the first 4 days after TBI.

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

Placebos will be prepared for the two experimental drugs and administered at identical time periods.

Placebo: 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.

Total Total of all reporting groups

Baseline Measures
    Drug     Placebo     Total  
Number of Participants  
[units: participants]
  7     7     14  
Age  
[units: participants]
     
<=18 years     7     7     14  
Between 18 and 65 years     0     0     0  
>=65 years     0     0     0  
Age  
[units: years]
Mean (Standard Deviation)
  8.6  (4.9)     9.7  (5.7)     9.1  (5.1)  
Gender  
[units: participants]
     
Female     1     3     4  
Male     6     4     10  
Region of Enrollment  
[units: participants]
     
United States     7     7     14  



  Outcome Measures
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1.  Primary:   Number of Participants Who Experienced Adverse Events   [ Time Frame: 14 days after drug administration ]

2.  Secondary:   Antioxidant Reserve   [ Time Frame: Within 5 days of injury ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Robert Clark
Organization: University of Pittsburgh
phone: 412-692-7260
e-mail: clarkrs@ccm.upmc.edu



Responsible Party: Robert Clark, MD, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01322009     History of Changes
Other Study ID Numbers: NS069247
1R01NS069247-01 ( US NIH Grant/Contract Award Number )
Study First Received: March 22, 2011
Results First Received: May 19, 2016
Last Updated: July 1, 2016
Health Authority: United States: Institutional Review Board