Overview

This trial has been completed.

Conditions traumatic brain injury, posttraumatic epilepsy
Treatments allopregnanolone injection, placebo injection
Phase phase 2
Sponsor University of California, Davis
Collaborator United States Department of Defense
Start date April 2013
End date May 2015
Trial size 13 participants
Trial identifier NCT01673828, DR081314

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Allopregnanolone injection (intravenous solution) continuous infusion for 5 days
allopregnanolone injection 3α,5α-tetrahydroprogesterone
Allopregnanolone intravenous solution in 0.9% sodium chloride injection with 6% sulfobutyl ether β-cyclodextrin sodium
(Placebo Comparator)
Placebo injection (intravenous solution) continuous infusion for 5 days
placebo injection Product P (placebo)
Placebo intravenous solution, 0.9% sodium chloride injection with 6% sulfobutyl ether β-cyclodextrin sodium

Primary Outcomes

Measure
Extended Glasgow Outcome Scale (GOS-E) Score
time frame: 3 months after injury

Secondary Outcomes

Measure
Mortality
time frame: 3 months after injury
Depression
time frame: 3 months after injury
Late Posttraumatic Epilepsy
time frame: 3 months after injury
Mortality
time frame: 6 months after injury
Extended Glasgow Outcome Scale (GOS-E) Score
time frame: 6 months after injury
Neurobehavioral Rating Scale Revised (NRS-R)
time frame: 6 months after injury
Test of Adult Reading
time frame: 6 months after injury
Tests of Executive Function
time frame: 6 months after injury
Tests of Learning, Delayed Recall, and Recognition
time frame: 6 months after injury
Test of Working Memory
time frame: 6 months after injury
Tests of Psychomotor and Processing Speed
time frame: 6 months after injury
Depression
time frame: 6 months after injury
Quality of Life
time frame: 6 months after injury
Late Posttraumatic Epilepsy
time frame: 6 months after injury
Late Posttraumatic Epilepsy
time frame: 12 months after injury
Anxiety
time frame: 6 months after injury

Eligibility Criteria

Male or female participants from 16 years up to 65 years old.

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

Additional Information

Official title A Double-blind, Placebo-controlled, Randomized Clinical Trial of Allopregnanolone for the Treatment of Traumatic Brain Injury
Principal investigator Michael A Rogawski, MD, PhD
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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by University of California, Davis.