Moderate Traumatic Brain Injury (TBI), Severe Traumatic Brain Injury
Conditions
Keywords
TBI, traumatic brain injury, VPA, valproic acid
Brief summary
The long-term goal of the clinical trial is to develop effective, safe, and easily administered life-saving treatments for patients with moderate to severe traumatic brain injury (TBI). Patients with moderate to severe TBI will randomly receive either: 1. Standard of care treatment and normal saline 2. Standard of care treatment and one dose of valproic acid (VPA) at a lower dose or a higher dose
Detailed description
The specific aim is to determine whether giving VPA at either a 50 mg/kg dose or a 100 mg/kg is safe (as measured by adverse events after treatment) in patients with moderate to severe TBI due to brain bruises.
Interventions
VPA (in 250 ml 0.9% sodium chloride solution)
OTHERStandard of care treatment + normal saline
Standard of care treatment + normal saline (0.9% sodium chloride solution) vehicle (250 ml)
Sponsors
United States Department of Defense
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Randomized, Placebo-Controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female between the ages of 18 and 65 years. 2. Body Mass Index between 18 kg/m2 and 35 kg/m2. 3. Females must be surgically sterilized, postmenopausal, or have a negative urine pregnancy test. 4. Moderate to severe TBI: Glasgow Coma Scale (GCS) 3-12. 5. Cerebral trauma confirmed on the initial CT scan with radiographic findings consistent with Brain Injury Guidelines category 3 (BIG3) criteria
Exclusion criteria
1. Persons with known history of adverse reactions to VPA 2. Persons with known history of hepatitis B or C or clinical history of hepatic dysfunction, pancreatitis, or renal insufficiency. 3. Persons with a known history of thrombocytopenia. 4. Persons with platelet count less than 100,000 per microliter of blood. 5. Persons with 2nd or 3rd degree burns of any size and location. 6. Female subjects who are pregnant or lactating. 7. Persons who are currently incarcerated or are in police custody. 8. Persons with inadequate venous access. 9. Treatment cannot start within 120 minutes from the onset of injury 10. Non-survivable injuries in the estimation of the attending trauma surgeon. 11. Interfacility transfers 12. The time of injury is unknown 13. Patients in hemorrhagic shock with a systolic blood pressure of \<90 mmHg on initial evaluation. 14. Persons with a known do not resuscitate order prior to randomization 15. Persons with a research opt out bracelet 16. Persons who are currently enrolled in another clinical trial. 17. Greater than 90 minutes between the onset of injury and arrival to the hospital
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Extended Glasgow Outcome Scale (GOS-E) | 3 months post-injury | Scoring values range from 1 to 8 with higher scores representing a better outcome. 1 indicates death, 2 indicates a vegetative state, 3 or 4 indicates severe disability, 5 or 6 indicates moderate disability, and 7 or 8 indicates good recovery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemorrhagic progression of the contusion (HPC) | First 24 hours post-injury as measured by a CT scan | We will quantify HPC as the change in volume of the largest contiguous brain lesion in mm. This will be measured through a comparison of the initial and the follow-up CT scan. |
| Disability Rating Score (DRS) | Discharge or day 7 and 3 months post-injury | This scale includes eight categories: A. Eye opening (0-5), B. Communication ability (0-4), C. Motor response (0-5), D. Feeding - cognitive ability only (0-3), E. Toileting - cognitive ability only (0-3), F. Grooming - cognitive ability only (0-3), G. Level of functioning - physical, mental, emotional or social function (0-5) and H. Employability - a full time worker, homemaker, or student (0-3). Higher scores in each category mean a worse outcome. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Disability Rating Score (DRS) | 6 months post-injury | This scale includes eight categories: A. Eye opening (0-5), B. Communication ability (0-4), C. Motor response (0-5), D. Feeding - cognitive ability only (0-3), E. Toileting - cognitive ability only (0-3), F. Grooming - cognitive ability only (0-3), G. Level of functioning - physical, mental, emotional or social function (0-5) and H. Employability - a full time worker, homemaker, or student (0-3). Higher scores in each category mean a worse outcome. |
| Extended Glasgow Outcome Scale (GOS-E) | 6 months post injury | Scoring values range from 1 to 8 with higher scores representing a better outcome. 1 indicates death, 2 indicates a vegetative state, 3 or 4 indicates severe disability, 5 or 6 indicates moderate disability, and 7 or 8 indicates good recovery. |
| Glasgow Coma Scale (GCS) | 24 hours post-injury | Evaluates three behavior responses: eye opening, best verbal and best motor. The following scoring is associated with responses: Eye opening response - Spontaneously 4, To speech 3, To pain 2 and No response 1; Best verbal - Oriented to time/place/person 5, Confused 4, Inappropriate words 3, Incomprehensible sounds 2 and No response 1; and Best motor response - Obeys commands 6, Moves to localized pain 5, Flexion withdrawal from pain 4, Abnormal flexion 3, Abnormal extension 2 and No response 1. The scoring is totaled with higher values associated with better response. Total Score: Best response=15, Comatose client=8 or less, and Totally unresponsive=3. |
Countries
United States
Contacts
Primary ContactHasan Alam, MD
Backup ContactNicole Meredyth, MD
Outcome results
None listed