Clinical Trial: Allopregnanolone for the Treatment of Traumatic Brain Injury

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Double-blind, Placebo-controlled, Randomized Clinical Trial of Allopregnanolone for the Treatment of Traumatic Brain Injury

Brief Summary: This study will provide initial data on the safety and effectiveness of allopregnanolone in improving neurobehavioral outcome and reducing mortality in adults with moderate and severe traumatic brain injury.

Detailed Summary: This is a double-blind, placebo-controlled, randomized, dose-finding, two-stage adaptive, clinical trial study comparing allopregnanolone to placebo when administered intravenously for 5 days beginning within 8 hours after injury. Test products to be administered are low and high dose allopregnanolone (Products L and H, respectively) and placebo (Product P) intravenous solutions. The products are administered during a 4-day treatment period followed by a 1-day dose de-escalation period. Stage 1 of the study will assess safety and confirm that dosing with Products L and H achieve the target steady-state plasma concentrations set for each of these products. Dosing will be adjusted in Stage 1, if necessary. Stage 2 will initially allocate subjects equally to Products L, H and P but will then use adaptive randomization to allocate subjects between Products L and H to optimized the probability of yielding a better 3-month Glasgow Outcome Score Extended (GOS-E) score.
Sponsor: University of California, Davis

Current Primary Outcome: Extended Glasgow Outcome Scale (GOS-E) Score [ Time Frame: 3 months after injury ]

GOS-E assessed by structured interview


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Mortality [ Time Frame: 3 months after injury ]
    Determination of mortality based on interviews with participant family members or a national death certificate search
  • Depression [ Time Frame: 3 months after injury ]
    Patient Health Questionaire (PHQ-9) assessed by structured interview
  • Late Posttraumatic Epilepsy [ Time Frame: 3 months after injury ]
    Presence of posttraumatic epilepsy assessed by structured interview
  • Mortality [ Time Frame: 6 months after injury ]
    Determination of mortality based on interviews with participant family members or a national death certificate search
  • Extended Glasgow Outcome Scale (GOS-E) Score [ Time Frame: 6 months after injury ]
    GOS-E assessed by structured interview
  • Neurobehavioral Rating Scale Revised (NRS-R) [ Time Frame: 6 months after injury ]
    NRS-R assessed by structured interview
  • Test of Adult Reading [ Time Frame: 6 months after injury ]
    Wechsler Test of Adult Reading (WTAR) assessed by structured interview
  • Tests of Executive Function [ Time Frame: 6 months after injury ]
    Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency and Color Word Interference, and Halstead-Reitan Battery Trails B, assessed by structured interview
  • Tests of Learning, Delayed Recall, and Recognition [ Time Frame: 6 months after injury ]
    Hopkins Verbal Learning-Revised (HVLT-R) and Brief Visual Memory Test-Revised (BVMT-R), assessed by structured interview
  • Test of Working Memory [ Time Frame: 6 months after injury ]
    Wechsler Adult Intelligence Scale-III (WAISIII) Number-Letter Sequencing assessed by structured interview
  • Tests of Psychomotor and Processing Speed [ Time Frame: 6 months after injury ]
    Symbol Digit Modalities Test (SDMT), Halstead-Reitan Battery Trails A, Grooved Pegboard, Simple Selection Attention Task (SSAT) and Complex Selection Attention Task (CSAT), assessed by structured interview
  • Depression [ Time Frame: 6 months after injury ]
    Patient Health Questionaire (PHQ-9) assessed by structured interview
  • Quality of Life [ Time Frame: 6 months after injury ]
    Short-form (SF-36) health survey assessed by structured interview
  • Late Posttraumatic Epilepsy [ Time Frame: 6 months after injury ]
    Presence of posttraumatic epilepsy assessed by structured interview
  • Late Posttraumatic Epilepsy [ Time Frame: 12 months after injury ]
    Presence of posttraumatic epilepsy assessed by structured interview
  • Anxiety [ Time Frame: 6 months after injury ]
    Beck Anxiety Inventory assessed by structure interview


Original Secondary Outcome:

  • Mortality [ Time Frame: 3 months after injury ]
    Determination of mortality based on interviews with participant family members or a national death certificate search
  • Depression [ Time Frame: 3 months after injury ]
    Patient Health Questionaire (PHQ-9) assessed by structured interview
  • Late Posttraumatic Epilepsy [ Time Frame: 3 months after injury ]
    Presence of posttraumatic epilepsy assessed by structured interview
  • Mortality [ Time Frame: 6 months after injury ]
    Determination of mortality based on interviews with participant family members or a national death certificate search
  • Extended Glasgow Outcome Scale (GOS-E) Score [ Time Frame: 6 months after injury ]
    GOS-E assessed by structured interview
  • Neurobehavioral Rating Scale Revised (NRS-R) [ Time Frame: 6 months after injury ]
    NRS-R assessed by structured interview
  • Test of Adult Reading [ Time Frame: 6 months after injury ]
    Wechsler Test of Adult Reading (WTAR) assessed by structured interview
  • Tests of Executive Function [ Time Frame: 6 months after injury ]
    Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency and Color Word Interference, and Halstead-Reitan Battery Trails B, assessed by structured interview
  • Tests of Learning, Delayed Recall, and Recognition [ Time Frame: 6 months after injury ]
    Hopkins Verbal Learning-Revised (HVLT-R) and Brief Visual Memory Test-Revised (BVMT-R), assessed by structured interview
  • Test of Working Memory [ Time Frame: 6 months after injury ]
    Wechsler Adult Intelligence Scale-III (WAISIII) Number-Letter Sequencing assessed by structured interview
  • Tests of Psychomotor and Processing Speed [ Time Frame: 6 months after injury ]
    Symbol Digit Modalities Test (SDMT), Halstead-Reitan Battery Trails A, Grooved Pegboard, Simple Selection Attention Task (SSAT) and Complex Selection Attention Task (CSAT), assessed by structured interview
  • Depression [ Time Frame: 6 months after injury ]
    Patient Health Questionaire (PHQ-9) assessed by structured interview
  • Quality of Life [ Time Frame: 6 months after injury ]
    SF-36 health survey assessed by structured interview
  • Late Posttraumatic Epilepsy [ Time Frame: 6 months after injury ]
    Presence of posttraumatic epilepsy assessed by structured interview
  • Late Posttraumatic Epilepsy [ Time Frame: 12 months after injury ]
    Presence of posttraumatic epilepsy assessed by structured interview
  • Anxiety [ Time Frame: 6 months after injury ]
    Beck Anxiety Inventory assessed by structure interview


Information By: University of California, Davis

Dates:
Date Received: August 20, 2012
Date Started: April 2013
Date Completion:
Last Updated: October 28, 2016
Last Verified: October 2016