外傷性脳損傷治療のためのバルプロ酸：VIBRANT前向き無作為化試験の試験プロトコル

Traumatic brain injury (TBI) carries significant mortality and morbidity in civilian and military populations. Current treatment guidelines for TBI are primarily supportive, and no pharmacological agent exists to attenuate the progression of brain injury. Valproic Acid (VPA) has long been used to treat neurological disorders; however, recent work has demonstrated its potential as a neuroprotective agent. We have already demonstrated that VPA administration in swine models of TBI (with or without associated hemorrhage and polytrauma) significantly improves survival and neurological recovery and decreases brain lesion size compared to controls. This paper introduces a phase 2/3 clinical trial that is designed to evaluate the efficacy and safety of VPA administration in patients with TBI.

In this randomized, double-blind, placebo-controlled, multicenter trial, patients with moderate to severe TBI (GCS 3-12) across nine level 1 trauma centers in the US will be randomized to receive either standard of care treatment and 250 mL of isotonic saline (control), or standard of care treatment and intravenous VPA at either 50 mg/kg (low-dose VPA group), or 100 mg/kg (high-dose VPA group). The primary endpoint of this clinical trial will be neurological status as measured by the Extended Glasgow Outcome Scale (GOS-E) 3 months post-TBI.

Our team has conducted multiple large animal studies that strongly support the cytoprotective effects of VPA treatment. The goal of this upcoming trial is to study the efficacy and safety of two doses of VPA in patients with moderate to severe TBI.

ClinicalTrials.gov, https://clinicaltrials.gov/study/NCT07166393, September 3, 2025.