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Allopregnanolone for the Treatment of Traumatic Brain Injury

Primary Purpose

Traumatic Brain Injury, Posttraumatic Epilepsy

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Allopregnanolone injection
Placebo injection
Sponsored by
Michael A. Rogawski, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Traumatic Brain Injury focused on measuring Brain Injuries, Pregnanolone, Epilepsy

Eligibility Criteria

16 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California, Davis Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Allopregnanolone

Placebo

Arm Description

Allopregnanolone injection (intravenous solution) continuous infusion for 5 days

Placebo injection (intravenous solution) continuous infusion for 5 days

Outcomes

Primary Outcome Measures

Extended Glasgow Outcome Scale (GOS-E) Score
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.

Secondary Outcome Measures

Full Information

First Posted
August 20, 2012
Last Updated
May 25, 2017
Sponsor
Michael A. Rogawski, MD, PhD
Collaborators
United States Department of Defense
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1. Study Identification

Unique Protocol Identification Number
NCT01673828
Brief Title
Allopregnanolone for the Treatment of Traumatic Brain Injury
Official Title
A Double-blind, Placebo-controlled, Randomized Clinical Trial of Allopregnanolone for the Treatment of Traumatic Brain Injury
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
April 2013 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Michael A. Rogawski, MD, PhD
Collaborators
United States Department of Defense

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury, Posttraumatic Epilepsy
Keywords
Brain Injuries, Pregnanolone, Epilepsy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Allopregnanolone
Arm Type
Experimental
Arm Description
Allopregnanolone injection (intravenous solution) continuous infusion for 5 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo injection (intravenous solution) continuous infusion for 5 days
Intervention Type
Drug
Intervention Name(s)
Allopregnanolone injection
Other Intervention Name(s)
3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one, Product L (allopregnanolone intravenous solution, low dose), Product H (allopregnanolone intravenous solution, high dose)
Intervention Description
Allopregnanolone intravenous solution in 0.9% sodium chloride injection with 6% sulfobutyl ether β-cyclodextrin sodium
Intervention Type
Drug
Intervention Name(s)
Placebo injection
Other Intervention Name(s)
Product P (placebo)
Intervention Description
Placebo intravenous solution, 0.9% sodium chloride injection with 6% sulfobutyl ether β-cyclodextrin sodium
Primary Outcome Measure Information:
Title
Extended Glasgow Outcome Scale (GOS-E) Score
Description
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.
Time Frame
6 months after injury

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael A Rogawski, MD, PhD
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
JoAnne E Natale, MD, PhD
Organizational Affiliation
University of California, Davis
Official's Role
Study Director
Facility Information:
Facility Name
University of California, Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Allopregnanolone for the Treatment of Traumatic Brain Injury

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