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Allopregnanolone for the Treatment of Traumatic Brain Injury

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01673828
Recruitment Status : Completed
First Posted : August 28, 2012
Results First Posted : June 28, 2017
Last Update Posted : June 28, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Posttraumatic Epilepsy Drug: Allopregnanolone injection Drug: Placebo injection Phase 2

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : April 2013
Primary Completion Date : May 2015
Study Completion Date : July 2016


Arms and Interventions

Arm Intervention/treatment
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)


Outcome Measures

Primary Outcome Measures :
  1. Extended Glasgow Outcome Scale (GOS-E) Score [ Time Frame: 6 months after injury ]
    GOS-E is a global scale for functional outcome that rates patient status into one of 8 levels. The minimum score is 1 and the maximum score is 8. 1 = dead; 2 = vegetative state; 3 = low severe disability; 4 = upper severe disability; 5 = low moderate disability; 6 = upper moderate disability; 7 = low good recovery; 8 = upper good recovery. GOS-E was assessed by 19 question structured interview.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 65 Years   (Child, Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01673828


Locations
United States, California
University of California, Davis Medical Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
Michael A. Rogawski, MD, PhD
United States Department of Defense
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

Responsible Party: Michael A. Rogawski, MD, PhD, Principal Invstigator, University of California, Davis
ClinicalTrials.gov Identifier: NCT01673828     History of Changes
Other Study ID Numbers: 273147
DR081314 ( Other Identifier: UC Davis )
First Posted: August 28, 2012    Key Record Dates
Results First Posted: June 28, 2017
Last Update Posted: June 28, 2017
Last Verified: May 2017

Keywords provided by Michael A. Rogawski, MD, PhD, University of California, Davis:
Brain Injuries
Pregnanolone
Epilepsy

Additional relevant MeSH terms:
Wounds and Injuries
Brain Injuries
Epilepsy
Brain Injuries, Traumatic
Epilepsy, Post-Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Pharmaceutical Solutions
Pregnanolone
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs