Moderate Traumatic Brain Injury (TBI)Phase 2/3VIBRANTNCT07166393
Valproic AcId for Traumatic BRAin INjury Trial
A Phase 2/3 study testing Valproic Acid (VPA) in people with Moderate Traumatic Brain Injury (TBI) and Severe Traumatic Brain Injury, run by Northwestern University at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Moderate Traumatic Brain Injury (TBI), Severe Traumatic Brain Injury
- What is being tested?
- Valproic Acid (VPA)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 432 participants
- Where
- 8 sitesUnited States
- Study dates
- May 2027to Dec 2031
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female between the ages of 18 and 65 years.
- Body Mass Index between 18 kg/m2 and 35 kg/m2.
- Females must be surgically sterilized, postmenopausal, or have a negative urine pregnancy test.
- Moderate to severe TBI: Glasgow Coma Scale (GCS) 3-12.
- Cerebral trauma confirmed on the initial CT scan with radiographic findings consistent with Brain Injury Guidelines category 3 (BIG 3) criteria
Who cannot join
- Persons with known history of adverse reactions to VPA
- Persons with known history of hepatitis B or C or clinical history of hepatic dysfunction, pancreatitis, or renal insufficiency.
- Persons with a known history of thrombocytopenia.
- Persons with platelet count less than 100,000 per microliter of blood.
- Persons with 2nd or 3rd degree burns of any size and location.
- Female subjects who are pregnant or lactating.
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- Persons who are currently incarcerated or are in police custody.
- Persons with inadequate venous access.
- Treatment cannot start within 120 minutes from the onset of injury
- Non-survivable injuries in the estimation of the attending trauma surgeon.
- Interfacility transfers
- The time of injury is unknown
- Patients in hemorrhagic shock with a systolic blood pressure of <90 mmHg on initial evaluation.
- Persons with a known "do not resuscitate" order prior to randomization
- Persons with a research "opt out" bracelet
- Persons who are currently enrolled in another clinical trial.
- Greater than 90 minutes between the onset of injury and arrival to the hospital
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
United States8 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Joel Rodgers, 205-515-3590, jrodgers@uabmc.edu
Jan Jansen, MD
University of Texas Southwestern
Dallas, Texas, 75390
Katherine Bosler, katherine.bosler@utsowthwestern.edu
Linda Dultz, MD
University of Southern California
Los Angeles, California, 90089-0701
Monica Wong, 323-409-8597, monica.wong@med.usc.edu
Matthew Martin, MD
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Madison Rundell, BS, mrundell@mcw.edu
Marc de Moya, MD
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Heather White, 615-421-2996, Heather.white@vumc.org
Amelia Maiga, MD
Oregon Health & Science University
Portland, Oregon, 97239
Samanatha Underwood, 503-494-5400, underwos@ohsu.edu
Mitchell Sally, MD
University of California, Davis
Sacramento, California, 95817
Shari Nichols, slnichols@health.ucdavis.edu
Rachael Callcut, MD
University of Arizona
Tucson, Arizona, 85719-4824
Robin Carlson, PhD, 520-626-2876, rscarlson@arizona.edu
Joseph Bellal, MD
About this study
Official title: Multi-institutional Phase 2/3 Trial of Valproic Acid in Patients With Moderate to Severe Traumatic Brain Injury
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:
- Standard of care treatment and normal saline
- Standard of care treatment and one dose of valproic acid (VPA) at a lower dose or a higher dose
Read the 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.
- Being tested
- Valproic Acid (VPA), Standard of care treatment + normal saline
- Keywords
- TBI, traumatic brain injury, VPA, valproic acid
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Valproic Acid (VPA)Drug
VPA (in 250 ml 0.9% sodium chloride solution)
Standard of care treatment + normal salineOther
Standard of care treatment + normal saline (0.9% sodium chloride solution) vehicle (250 ml)
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | Standard of Care + Normal Saline (0.9% sodium chloride solution) Receives: Other: Standard of care treatment + normal saline |
| Experimental | Experimental | 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 Receives: Drug: Valproic Acid (VPA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Extended Glasgow Outcome Scale (GOS-E)
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.
Measured: 3 months post-injury
Secondary outcomes (2)
Hemorrhagic progression of the contusion (HPC)
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.
Measured: First 24 hours post-injury as measured by a CT scan
Disability Rating Score (DRS)
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.
Measured: Discharge or day 7 and 3 months post-injury
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2025
- Study startMay 2027 (estimated)
- Primary completionMay 2031 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Moderate Traumatic Brain Injury (TBI)Studies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, Placebo-Controlled
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 432 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Principal investigator, Hasan Alam, Northwestern University
- Investigators
- Hasan Alam, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07166393
- Sponsor's protocol ID
- STU00223546
- Other IDs
- HT9425-24-1-0241
- Acronym
- VIBRANT
- Status last verified
- Aug 2026
- First submitted
- 3 Sep 2025
- Last updated
- 13 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Aggregate data will be shared.
Publications
Visa MA, Liggett MR, Lashley S, Bhatti U, Dawood ZA, Anand A, Gill NP, Scholtens DM, Wang B, Alam HB. Valproic acid for treatment of traumatic brain injury: Study protocol for the VIBRANT prospective randomized trial. Transfusion. 2026 May;66 Suppl 1(Suppl 1):S266-S277. doi: 10.1111/trf.70029. Epub 2025 Dec 20.
PubMed 41420823
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-institutional Phase 2/3 Trial of Valproic Acid in Patients With Moderate to Severe Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT07166393
- Acronym / sponsor ID
- VIBRANT / STU00223546
- Keywords
- TBI, traumatic brain injury, VPA, valproic acid
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 432 participants (estimated)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- May 2027 (estimated)
- Primary completion
- May 2031 (estimated)
- Study completion
- Dec 2031 (estimated)
- First posted
- 10 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Standard of care treatment and normal saline
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Randomized, Placebo-Controlled
| Arm | Type | Receives |
|---|---|---|
| Control | Placebo comparator | Other: Standard of care treatment + normal salineStandard of Care + Normal Saline (0.9% sodium chloride solution) |
| Experimental | Experimental | Drug: 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female between the ages of 18 and 65 years.
- Body Mass Index between 18 kg/m2 and 35 kg/m2.
- Females must be surgically sterilized, postmenopausal, or have a negative urine pregnancy test.
- Moderate to severe TBI: Glasgow Coma Scale (GCS) 3-12.
- Cerebral trauma confirmed on the initial CT scan with radiographic findings consistent with Brain Injury Guidelines category 3 (BIG 3) criteria
Key exclusion criteria (17 listed)
- Persons with known history of adverse reactions to VPA
- Persons with known history of hepatitis B or C or clinical history of hepatic dysfunction, pancreatitis, or renal insufficiency.
- Persons with a known history of thrombocytopenia.
- Persons with platelet count less than 100,000 per microliter of blood.
- Persons with 2nd or 3rd degree burns of any size and location.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Valproic Acid (VPA)VPA (in 250 ml 0.9% sodium chloride solution) | Drug | Experimental |
| Standard of care treatment + normal salineStandard of care treatment + normal saline (0.9% sodium chloride solution) vehicle (250 ml) | Other | Control |
Primary outcome
Extended Glasgow Outcome Scale (GOS-E)
Time frame: 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.
2 secondary outcomes
Hemorrhagic progression of the contusion (HPC)
Time frame: First 24 hours post-injury as measured by a CT scan
Disability Rating Score (DRS)
Time frame: Discharge or day 7 and 3 months post-injury
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
- Derived from this study: PubMed 41420823Visa MA, Liggett MR, Lashley S, Bhatti U, Dawood ZA, Anand A, Gill NP, Scholtens DM, Wang B, Alam HB. Valproic acid for treatment of traumatic brain injury: Study protocol for the VIBRANT prospective randomized trial. Transfusion. 2026 May;66 Suppl 1(Suppl 1):S266-S277. doi: 10.1111/trf.70029. Epub 2025 Dec 20.
- Individual participant dataSharing planned: No. Aggregate data will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Hasan Alam, MD principal investigator
Northwestern University
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Valproic Acid (VPA) in people with Moderate Traumatic Brain Injury (TBI) and Severe Traumatic Brain Injury, run by Northwestern University at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hasan Alam, MD (312-926-4962, Hasan.Alam@nm.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Extended Glasgow Outcome Scale (GOS-E) (time frame: 3 months post-injury). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07166393, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2026.