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Traumatic Neuroprotection and Epilepsy Prevention of Valproate Acid (VPA)

Primary Purpose

Traumatic Brain Injury

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

valproate acid

About this trial

This is an interventional prevention trial for Traumatic Brain Injury focused on measuring valproate acid, traumatic brain injury, brain protection, epilepsy

Eligibility Criteria

16 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Institute of Neurosurgery, Xijing Hospital, Fourth Military Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

valproate acid

placebo

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

brain MRI scan

Brain MRI scan is applied to monitor the degree and progress of the brain damage.

the blood concentration of VPA

the blood was collected to detect the concentration about 2 hours after the medication of VPA

Full Information

NCT ID

NCT02027987

First Posted

October 28, 2013

Last Updated

January 2, 2014

Sponsor

Xijing Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02027987

Brief Title

Traumatic Neuroprotection and Epilepsy Prevention of Valproate Acid

Acronym

VPA

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2013

Overall Recruitment Status

Unknown status

Study Start Date

October 2013 (undefined)

Primary Completion Date

December 2016 (Anticipated)

Study Completion Date

December 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Xijing Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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). 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). 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Traumatic Brain Injury

Keywords

valproate acid, traumatic brain injury, brain protection, epilepsy

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

valproate acid

Arm Type

Experimental

Arm Description

Arm Title

placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

valproate acid

Other Intervention Name(s)

Sodium valproate

Intervention Description

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

Primary Outcome Measure Information:

Title

DRS scores

Description

Time Frame

On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study

Secondary Outcome Measure Information:

Title

the time of break out and state of epilepsy

Description

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.

Time Frame

from 0 to 42 days when the epilepsy break out

Title

brain MRI scan

Description

Brain MRI scan is applied to monitor the degree and progress of the brain damage.

Time Frame

6 weeks after treatment

Title

the blood concentration of VPA

Description

the blood was collected to detect the concentration about 2 hours after the medication of VPA

Time Frame

On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study

Other Pre-specified Outcome Measures:

Title

CRS-R score

Description

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.

Time Frame

On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study

Title

function of kidney

Description

There are three main indicators: blood creatinine, urea nitrogen, and uric acid. These indicator are used as a monitor of the kidney safety.

Time Frame

On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study

Title

function of liver

Description

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.

Time Frame

On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study

Title

Physiological and pathological reflex check

Time Frame

On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study

Title

muscular strength and tension test

Description

There are 6 grades in muscular strength test. And muscular tension test was referred to Modified Ashworth scale.

Time Frame

On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study

10. Eligibility

Sex

All

Minimum Age & Unit of Time

16 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

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

Phone

086-29-84773307

hushijie@fmmu.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

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

Phone

086 13992888996

hushijie1979@126.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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

Organizational Affiliation

Institute of Neurosurgery, Xijing Hospital, Fourth Military Medical University

Official's Role

Study Director

Facility Information:

Facility Name

Institute of Neurosurgery, Xijing Hospital, Fourth Military Medical University

City

Xi'an City

State/Province

Shaanxi

ZIP/Postal Code

710032

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

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

Phone

086 029 84773307

hushijie@fmmu.edu.cn

First Name & Middle Initial & Last Name & Degree

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

Phone

086 029 13992888996

feizhou@fmmu.edu.cn

First Name & Middle Initial & Last Name & Degree

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

12. IPD Sharing Statement

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Traumatic Neuroprotection and Epilepsy Prevention of Valproate Acid

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