Allopregnanolone for the Treatment of Traumatic Brain Injury

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by University of California, Davis
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, Davis
ClinicalTrials.gov Identifier:
NCT01673828
First received: August 20, 2012
Last updated: May 22, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Traumatic Brain Injury
Posttraumatic Epilepsy
Drug: Allopregnanolone injection
Drug: Placebo injection
Phase 2

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

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Extended Glasgow Outcome Scale (GOS-E) Score [ Time Frame: 3 months after injury ] [ Designated as safety issue: No ]
    GOS-E assessed by structured interview


Secondary Outcome Measures:
  • Mortality [ Time Frame: 3 months after injury ] [ Designated as safety issue: No ]
    Determination of mortality based on interviews with participant family members or a national death certificate search

  • Depression [ Time Frame: 3 months after injury ] [ Designated as safety issue: No ]
    Patient Health Questionaire (PHQ-9) assessed by structured interview

  • Late Posttraumatic Epilepsy [ Time Frame: 3 months after injury ] [ Designated as safety issue: No ]
    Presence of posttraumatic epilepsy assessed by structured interview

  • Mortality [ Time Frame: 6 months after injury ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    GOS-E assessed by structured interview

  • Neurobehavioral Rating Scale Revised (NRS-R) [ Time Frame: 6 months after injury ] [ Designated as safety issue: No ]
    NRS-R assessed by structured interview

  • Test of Adult Reading [ Time Frame: 6 months after injury ] [ Designated as safety issue: No ]
    Wechsler Test of Adult Reading (WTAR) assessed by structured interview

  • Tests of Executive Function [ Time Frame: 6 months after injury ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Patient Health Questionaire (PHQ-9) assessed by structured interview

  • Quality of Life [ Time Frame: 6 months after injury ] [ Designated as safety issue: No ]
    Short-form (SF-36) health survey assessed by structured interview

  • Late Posttraumatic Epilepsy [ Time Frame: 6 months after injury ] [ Designated as safety issue: No ]
    Presence of posttraumatic epilepsy assessed by structured interview

  • Late Posttraumatic Epilepsy [ Time Frame: 12 months after injury ] [ Designated as safety issue: No ]
    Presence of posttraumatic epilepsy assessed by structured interview

  • Anxiety [ Time Frame: 6 months after injury ] [ Designated as safety issue: No ]
    Beck Anxiety Inventory assessed by structure interview


Estimated Enrollment: 136
Study Start Date: April 2013
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allopregnanolone
Allopregnanolone injection (intravenous solution) continuous infusion for 5 days
Drug: Allopregnanolone injection
Allopregnanolone intravenous solution in 0.9% sodium chloride injection with 6% sulfobutyl ether β-cyclodextrin sodium
Other Names:
  • 3α,5α-tetrahydroprogesterone
  • 3α-hydroxy-5α-pregnan-20-one
  • Product L (allopregnanolone intravenous solution, low dose)
  • Product H (allopregnanolone intravenous solution, high dose)
Placebo Comparator: Placebo
Placebo injection (intravenous solution) continuous infusion for 5 days
Drug: Placebo injection
Placebo intravenous solution, 0.9% sodium chloride injection with 6% sulfobutyl ether β-cyclodextrin sodium
Other Name: Product P (placebo)

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   16 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • English or Spanish speaking person
  • Moderate to severe closed or blunt traumatic brain injury [post resuscitation Glasgow Coma Score (GCS) 3-12 with abnormal head CT scan if GCS is 9-12]
  • Less than 8 hours from injury to study initiation
  • Able to participate for the full term of the study

Exclusion Criteria:

  • Subjects with life expectancy of less than 24 hours
  • Isolated epidural hematoma
  • Hypoxia (pulse oximetry saturation ≤90% for 15 or more minutes before enrollment)
  • Hypotension (systolic blood pressure ≤90 mm Hg on 2 or more reliable measurements before enrollment)
  • Cardiopulmonary arrest prior to randomization
  • Spinal cord injury with motor deficits
  • Bilateral non-reactive pupils with Glasgow Coma Scale 3
  • Body weight >120 kg
  • Pregnancy
  • Active breast or reproductive organ cancer
  • Allergy to progesterone
  • History of thromboembolic events
  • Receipt of activated Factor VII before enrollment
  • Any disease that is unstable or which could jeopardize the safety of the subject including severe renal impairment (creatinine clearance <50 ml/min)
  • Prisoner/ward of the state
  • Known treatment with another investigational drug therapy or procedure within 30 days of injury
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01673828

Locations
United States, California
University of California, Davis Medical Center Recruiting
Sacramento, California, United States, 95817
Contact: Nancy Rudisill    916-816-4824    nancy.rudisill@ucdmc.ucdavis.edu   
Contact: Steffany Lim    9167346265    steffany.lim@ucdmc.ucdavis.edu   
Principal Investigator: Michael A Rogawski, MD, PhD         
Sub-Investigator: JoAnne E Natale, MD, PhD         
Sponsors and Collaborators
University of California, Davis
Investigators
Principal Investigator: Michael A Rogawski, MD, PhD University of California, Davis
Study Director: JoAnne E Natale, MD, PhD University of California, Davis
  More Information

No publications provided

Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT01673828     History of Changes
Other Study ID Numbers: DR081314
Study First Received: August 20, 2012
Last Updated: May 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, Davis:
Brain Injuries
Pregnanolone
Epilepsy

Additional relevant MeSH terms:
Epilepsy
Epilepsy, Post-Traumatic
Brain Injuries
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Pregnanolone
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014