Allopregnanolone for the Treatment of Traumatic Brain Injury

Traumatic Brain Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01673828
• Other study ID #: DR081314
• Status: Completed
• Phase: Phase 2
• First received: August 20, 2012
• Last updated: October 28, 2016
• Start date: April 2013
• Est. completion date: July 2016

Study information

• Verified date: October 2016
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: July 2016
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Injuries
• Epilepsy
• Epilepsy, Post-Traumatic
• Posttraumatic Epilepsy
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Drug:
• Allopregnanolone injection
Allopregnanolone intravenous solution in 0.9% sodium chloride injection with 6% sulfobutyl ether ß-cyclodextrin sodium
• Placebo injection
Placebo intravenous solution, 0.9% sodium chloride injection with 6% sulfobutyl ether ß-cyclodextrin sodium

Locations

Country	Name	City	State
United States	University of Southern California	Los Angeles	California
United States	University of California, Davis Medical Center	Sacramento	California
United States	University of California, San Diego	San Diego	California
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Davis	United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Extended Glasgow Outcome Scale (GOS-E) Score	GOS-E assessed by structured interview	3 months after injury	No
Secondary	Mortality	Determination of mortality based on interviews with participant family members or a national death certificate search	3 months after injury	No
Secondary	Depression	Patient Health Questionaire (PHQ-9) assessed by structured interview	3 months after injury	No
Secondary	Late Posttraumatic Epilepsy	Presence of posttraumatic epilepsy assessed by structured interview	3 months after injury	No
Secondary	Mortality	Determination of mortality based on interviews with participant family members or a national death certificate search	6 months after injury	No
Secondary	Extended Glasgow Outcome Scale (GOS-E) Score	GOS-E assessed by structured interview	6 months after injury	No
Secondary	Neurobehavioral Rating Scale Revised (NRS-R)	NRS-R assessed by structured interview	6 months after injury	No
Secondary	Test of Adult Reading	Wechsler Test of Adult Reading (WTAR) assessed by structured interview	6 months after injury	No
Secondary	Tests of Executive Function	Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency and Color Word Interference, and Halstead-Reitan Battery Trails B, assessed by structured interview	6 months after injury	No
Secondary	Tests of Learning, Delayed Recall, and Recognition	Hopkins Verbal Learning-Revised (HVLT-R) and Brief Visual Memory Test-Revised (BVMT-R), assessed by structured interview	6 months after injury	No
Secondary	Test of Working Memory	Wechsler Adult Intelligence Scale-III (WAISIII) Number-Letter Sequencing assessed by structured interview	6 months after injury	No
Secondary	Tests of Psychomotor and Processing Speed	Symbol Digit Modalities Test (SDMT), Halstead-Reitan Battery Trails A, Grooved Pegboard, Simple Selection Attention Task (SSAT) and Complex Selection Attention Task (CSAT), assessed by structured interview	6 months after injury	No
Secondary	Depression	Patient Health Questionaire (PHQ-9) assessed by structured interview	6 months after injury	No
Secondary	Quality of Life	Short-form (SF-36) health survey assessed by structured interview	6 months after injury	No
Secondary	Late Posttraumatic Epilepsy	Presence of posttraumatic epilepsy assessed by structured interview	6 months after injury	No
Secondary	Late Posttraumatic Epilepsy	Presence of posttraumatic epilepsy assessed by structured interview	12 months after injury	No
Secondary	Anxiety	Beck Anxiety Inventory assessed by structure interview	6 months after injury	No