Valproic Acid for Traumatic Brain Injury

(VIBRANT Trial)

Not yet recruiting at 7 trial locations

Overseen By Hasan Alam, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Northwestern University

Disqualifiers: Hepatitis, Pancreatitis, Renal insufficiency, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to identify effective and easy-to-use treatments for individuals with moderate to severe traumatic brain injury (TBI). Participants will receive either the usual medical care plus a saline solution or the usual care plus valproic acid (a medication used to treat seizures) at one of two different doses. It suits those who have experienced a significant head injury confirmed by a CT scan that affects their daily life. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in TBI care.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that valproic acid (VPA) might help treat traumatic brain injury (TBI). In animal studies, VPA was safe and reduced the size of brain injuries, suggesting it could protect the brain and aid recovery.

However, there are some risks. VPA can sometimes harm the nervous system, though this does not occur in everyone. For some patients, the benefits might outweigh the risks.

In this trial, researchers are testing two doses of VPA—50 mg/kg and 100 mg/kg—to assess their safety in humans. The trial's phase indicates that earlier studies have shown some safety for VPA, but further testing is needed to confirm this. It is important to consider these factors and consult a doctor before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for TBI?

Unlike the standard of care for traumatic brain injury, which often involves supportive treatments like monitoring intracranial pressure and managing symptoms, Valproic Acid (VPA) offers a different approach. Researchers are excited about VPA because it acts as a neuroprotective agent, potentially reducing brain damage by stabilizing cell membranes and preventing cell death. Additionally, VPA is already well-known for its use in epilepsy, suggesting a favorable safety profile. The possibility of administering VPA shortly after injury could offer a timely intervention that current treatments lack, providing new hope for improved recovery outcomes.

What evidence suggests that valproic acid might be an effective treatment for traumatic brain injury?

Research has shown that valproic acid (VPA) can help treat traumatic brain injury (TBI). In this trial, participants in the experimental arm will receive standard care treatment plus one dose of VPA. Studies have found that a single dose of VPA can improve brain function and reduce the size of brain damage in TBI patients. VPA also decreases brain swelling three days after the injury. It reaches the injured areas of the brain and protects them, aiding in recovery. These findings suggest that VPA could be a promising treatment for lessening the effects of moderate to severe TBI. ^{1 2 4 6 7}

Who Is on the Research Team?

Hasan Alam, MD

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for individuals with moderate to severe traumatic brain injury. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be excluded based on factors like other medical conditions or treatments that could interfere with the study.

Inclusion Criteria

Body Mass Index between 18 kg/m2 and 35 kg/m2

Cerebral trauma confirmed on the initial CT scan with radiographic findings consistent with Brain Injury Guidelines category 3 (BIG3) criteria

I am between 18 and 65 years old.

Exclusion Criteria

Persons who are currently incarcerated or are in police custody

Persons with known history of adverse reactions to VPA

Persons with platelet count less than 100,000 per microliter of blood

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive standard of care treatment and either normal saline or one dose of valproic acid (VPA) at a lower or higher dose

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments using the Glasgow Coma Scale and Disability Rating Score

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Valproic Acid

Trial Overview The trial is testing whether adding valproic acid (VPA) to standard care improves outcomes in patients with traumatic brain injury. Participants will either receive standard treatment plus normal saline or standard treatment plus one dose of VPA at a low or high dose.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 1 Intervention

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

Group II: Control Placebo Group 1 Intervention

Standard of Care + Normal Saline (0.9% sodium chloride solution)

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8715863/

A Single Dose of Valproic Acid Improves Neurologic ... In this clinically relevant model of isolated TBI, a single dose of VPA attenuates neurological impairment and decreases brain lesion size.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07166393

Valproic AcId for Traumatic BRAin INjury Trial 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 ...

3. frontiersin.org frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2018.00117/full

Valproic Acid Attenuates Traumatic Brain Injury-Induced ... (A) VPA treatment improved neurological functions after TBI. (B) VPA treatment decreased brain water content 3 days after TBI (p < 0.05).

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1064748125002313

A CASE REPORT ON POST-TBI SEIZURE MANAGEMENT ... Valproic acid, while effective for treating various neurological conditions, poses significant risks of neurotoxicity, particularly through mechanisms ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7830776/

Valproic Acid Treatment Rescues Injured Tissues After ... VPA penetrates injured brain tissues, and exerts neuroprotective and pro-survival effects that resulted in a significant reduction in brain lesion size after ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10498971/

A Retrospective Case Series on Valproic Acid for Early ... Purpose: Early post-traumatic seizures occur within 7 days following a traumatic brain injury and may lead to additional brain damage and poor outcomes.

7. scholars.duke.edu scholars.duke.edu/individual/pub1606774

Valproic acid decreases brain lesion size and improves ... In swine subjected to TBI, hemorrhagic shock, and polytrauma, VPA treatment is safe, decreases brain lesion size, and reduces neurologic injury.