Traumatic Neuroprotection and Epilepsy Prevention of Valproate Acid

NCT ID: NCT02027987

Last Updated: 2014-01-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2016-12-31

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.

Conditions

Traumatic Brain Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

valproate acid

The patients began receiving treatment at a dose of 400 mg VPA twice daily on the day after randomization by intravenous drip, with this dose continued for 14 days.The dose was increased to 500 mg twice daily at week 3 and to 400 mg three times daily at week 4 if the DRS score had not improved by at least 2 points from baseline. After the week 4 assessment, the study drug was tapered over a period of 2 to 3 days, with assessment of the patients continued through week 6. Additional procedural details are provided in the study protocol.

Group Type: EXPERIMENTAL

valproate acid

Intervention Type: DRUG

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

placebo

Group Type: PLACEBO_COMPARATOR

No interventions assigned to this group

Interventions

valproate acid

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

Intervention Type: DRUG

Other Intervention Names

Sodium valproate

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.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xijing Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fei Zhou, M.D., Ph.D.

Role: STUDY_DIRECTOR

Institute of Neurosurgery, Xijing Hospital, Fourth Military Medical University

Locations

Institute of Neurosurgery, Xijing Hospital, Fourth Military Medical University

Xi'an, Shaanxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

Hu S Jie, M.D., Ph.D.

Role: CONTACT

hushijie@fmmu.edu.cn

086-29-84773307

Hu S Jie, M.D., Ph.D.

Role: CONTACT

hushijie1979@126.com

086 13992888996

Facility Contacts

Hu S Jie, M.D., Ph.D.

Role: primary

hushijie@fmmu.edu.cn

086 029 84773307

Fei Zhou, M.D., Ph.D.

Role: backup

feizhou@fmmu.edu.cn

086 029 13992888996

Other Identifiers

20130814-7

Identifier Type: -

Identifier Source: org_study_id