Valproic AcId for Traumatic BRAin INjury Trial

Not Applicable

Not yet recruiting

• Conditions: Moderate Traumatic Brain Injury (TBI); Severe Traumatic Brain Injury
• Interventions: Other: Standard of care treatment + normal saline; Drug: Valproic Acid (VPA)

• Registration Number: NCT07166393
• Lead Sponsor: Northwestern University

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.

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-03
• Study First Submitted QC: 2025-09-03
• Study First Posted: 2025-09-10
• Last Update Submitted: 2025-09-16
• Last Update Posted: 2025-09-22
• Study Start: 2026-05-01
• Primary Completion: 2030-02
• Study Completion: 2030-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 432

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Standard of care treatment + normal saline	Standard of Care + Normal Saline (0.9% sodium chloride solution)
Experimental	Valproic Acid (VPA)	Standard of care treatment + one dose of VPA (in 250 ml 0.9% sodium chloride solution) in the following two doses: * Lower dose VPA: 50 mg/kg * Higher dose VPA: 100 mg/kg

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (8)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of Arizona; 🇺🇸 Tucson, Arizona, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

University of California, Davis; 🇺🇸 Sacramento, California, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

University of Texas Southwestern; 🇺🇸 Dallas, Texas, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States