Traumatic Neuroprotection and Epilepsy Prevention of Valproate Acid

Traumatic Brain Injury Clinical Trial

— VPA  

Official title:

Clinical Study on the Neuroprotection and Epilepsy Prevention of Valproate Acid Administered After Severe Traumatic Brain Injury

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02027987
• Other study ID #: 20130814-7
• Status: Recruiting
• Phase: Phase 1
• First received: October 28, 2013
• Last updated: January 2, 2014
• Start date: October 2013
• Est. completion date: December 2016

Study information

• Verified date: November 2013
• Source: Xijing Hospital
• Contact: Hu S Jie, M.D., Ph.D.
• Phone: 086-29-84773307
• Email: hushijie[@]fmmu.edu.cn
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Brain Injuries
• Traumatic Brain Injury

Intervention

Drug:
• valproate acid
valproate acid is a common drug which is applied for epilepsy prevention and treatment.

Locations

Country	Name	City	State
China	Institute of Neurosurgery, Xijing Hospital, Fourth Military Medical University	Xi'an City	Shaanxi

Sponsors (1)

Lead Sponsor	Collaborator
Xijing Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CRS-R score	The CRS-R score is a standardized neurobehavioral assessment tool comprising six hierarchically organized subscales (i.e., auditory, visual, motor, oromotor-verbal, communication, and arousal); scores range from 0 to 23, with higher scores indicating a higher level of neurobehavioral function.	On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study	Yes
Other	function of kidney	There are three main indicators: blood creatinine, urea nitrogen, and uric acid. These indicator are used as a monitor of the kidney safety.	On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study	Yes
Other	function of liver	There are several main indicators including ALT, AST, Tbil, D-bil, I-bil, ALB,GLB, and ALP, and so on. These indicators could monitor the change of liver function in case of liver damage.	On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study	Yes
Other	Physiological and pathological reflex check		On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study	Yes
Other	muscular strength and tension test	There are 6 grades in muscular strength test. And muscular tension test was referred to Modified Ashworth scale.	On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study	Yes
Primary	DRS scores	The DRS score includes measures of eye opening, verbalization, and motor response (derived from the Glasgow Coma Scale); cognitive understanding of feeding, dressing, and grooming; degree of assistance and supervision required; and employability. Scores range from 0 to 29, with higher values indicating greater disability.	On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study	Yes
Secondary	the time of break out and state of epilepsy	When the patient were admitted into the study, the breakout and the severity of epilepsy would be monitored and treated until the end of the trial.	from 0 to 42 days when the epilepsy break out	Yes
Secondary	brain MRI scan	Brain MRI scan is applied to monitor the degree and progress of the brain damage.	6 weeks after treatment	Yes
Secondary	the blood concentration of VPA	the blood was collected to detect the concentration about 2 hours after the medication of VPA	On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study	Yes