Allopregnanolone for the Treatment of Traumatic Brain Injury

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

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.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury; Posttraumatic Epilepsy
• Intervention / Treatment: Drug: Allopregnanolone injection; Drug: Placebo injection

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 Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: Product P (placebo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 months after injury

Collaborators and Investigators

• Sponsor: Michael A. Rogawski, MD, PhD
• Collaborators: 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

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: August 20, 2012
• First Submitted That Met QC Criteria: August 27, 2012
• First Posted (Estimate): August 28, 2012

Study Record Updates

• Last Update Posted (Actual): June 28, 2017
• Last Update Submitted That Met QC Criteria: May 25, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Epilepsy; Brain Injuries; Pregnanolone
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Epilepsy; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Epilepsy, Post-Traumatic; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics; Pharmaceutical Solutions; Pregnanolone
• Other Study ID Numbers: 273147; DR081314 (Other Identifier: UC Davis)