Clinical trial NCT02027987: Traumatic Neuroprotection and Epilepsy Prevention of Valproate Acid
Official title: Clinical Study on the Neuroprotection and Epilepsy Prevention of Valproate Acid Administered After Severe Traumatic Brain Injury
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Traumatic Brain Injury
Keywords: valproate acid
traumatic brain injury
brain protection
epilepsy
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
First posted: 2014-01-06
Enrollment: 160
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 1. Background:

   Preliminary studies have suggested that valproate acid (VPA) may promote neuron survival, inhibit apoptosis, decrease the neuron function deficit in cerebral ischemia, and promote the brain functional recovery after traumatic brain injury (TBI). Besides, in the guide of prevention and treatment of epilepsy in 2007, VPA was one of the antiepileptic drugs which were suggested to prevent early epilepsy after TBI (less than 7 days).
2. Objectives:

   Our main objective was to evaluate whether VPA could protect brain and improve recovery of brain function after severe TBI. The secondary objective was to explore whether VPA could prevent late epilepsy after severe TBI (more than 7 days).
3. Methods:

We would enroll 160 patients who were in a vegetative or minimally conscious state 4 to 16 weeks after TBI and who were receiving inpatient rehabilitation. Patients were randomly assigned to receive VPA or placebo for 4 weeks and were followed for 2 weeks after the treatment was discontinued. The rate of functional recovery on the Disability Rating Scale (DRS; range, 0 to 29, with higher scores indicating greater disability) was compared over the 4 weeks of treatment (primary outcome) and during the 2-week washout period with the use of mixed-effects regression models.


Eligibility criteria: Inclusion Criteria:

* Eligible patients were 16 to 65 years of age with all genders.
* The patients had sustained a nonpenetrating traumatic brain injury 4 to 16 weeks before enrollment, with the confirmation of CT or MRI.
* Additional eligibility criteria were a vegetative state or a minimally conscious state, as indicated by a Disability Rating Scale (DRS) score greater than 11.
* There was an inability both to follow commands consistently and to engage in functional communication, as assessed by the score on the Coma Recovery Scale-Revised (CRS-R)
* All the patients had provided written informed consent.
* The patients were receiving usual inpatient rehabilitation and treatment at each site.

Exclusion Criteria:

* unstable health state,including:Be allergic to VPA, or with serious allergic diseases or allergic constitutions;With serious cardiovascular diseases, hepatic, renal, or psychiatric diseases;With serious respiratory, endocrine, or blood system diseases;With serious infections or malignant tumors; With weakened immunologic status;Addison's diseases;With alcohol or drug abuse.
* Any disability related to the central nervous system that predated the traumatic brain injury.
* Pregnancy or breastfeeding females.
* More than one seizure in the previous month.
* Prior treatment with VPA
* In the case of patients who were undergoing evaluation for ventricular shunt placement or receiving a psychoactive medication, enrollment was deferred until shunt placement had been completed or psychoactive medications discontinued.
* The patients had enrolled the other studies in the past three months or are engaging the other studies.
* The patients were assessed as unqualified for the study according to the comprehensive evaluation opinion brought forward by the research team.

Primary outcomes:
measure: DRS scores
timeFrame: On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study
Secondary outcomes:
measure: the time of break out and state of epilepsy
timeFrame: from 0 to 42 days when the epilepsy break out
measure: brain MRI scan
timeFrame: 6 weeks after treatment
measure: the blood concentration of VPA
timeFrame: On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study
Other outcomes:
measure: CRS-R score
timeFrame: On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study
measure: function of kidney
timeFrame: On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study
measure: function of liver
timeFrame: On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study
measure: Physiological and pathological reflex check
timeFrame: On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study
measure: muscular strength and tension test
timeFrame: On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study
Locations:
city: Xi'an City
country: China
facility: Institute of Neurosurgery, Xijing Hospital, Fourth Military Medical University
state: Shaanxi
Study officials:
affiliation: Institute of Neurosurgery, Xijing Hospital, Fourth Military Medical University
name: Fei Zhou, M.D., Ph.D.
role: STUDY_DIRECTOR
References: