Clinical trial NCT01673828: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Traumatic Brain Injury
Posttraumatic Epilepsy
Keywords: Brain Injuries
Pregnanolone
Epilepsy
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2012-08-28
Enrollment: 13
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Extended Glasgow Outcome Scale (GOS-E) Score
timeFrame: 6 months after injury
Secondary outcomes:
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
Study officials:
affiliation: University of California, Davis
name: Michael A Rogawski, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Davis
name: JoAnne E Natale, MD, PhD
role: STUDY_DIRECTOR
References: