Traumatic Brain InjuryPhase 1VPANCT02027987
Traumatic Neuroprotection and Epilepsy Prevention of Valproate Acid
A Phase 1 study testing valproate acid in people with Traumatic Brain Injury, run by Xijing Hospital at 1 site in China.
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). Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- valproate acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteChina
- Study dates
- Oct 2013to Dec 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Institute of Neurosurgery, Xijing Hospital, Fourth Military Medical University
Xi'an, Shaanxi, 710032
Hu S Jie, M.D., Ph.D., 086 029 84773307, hushijie@fmmu.edu.cn
Fei Zhou, M.D., Ph.D., 086 029 13992888996, feizhou@fmmu.edu.cn
About this study
Official title: Clinical Study on the Neuroprotection and Epilepsy Prevention of Valproate Acid Administered After Severe Traumatic Brain Injury
- 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.
- Conditions
- Traumatic Brain Injury
- Being tested
- valproate acid
- Keywords
- valproate acid, traumatic brain injury, brain protection, epilepsy
- Medical subject headings
- Brain Injuries, Traumatic, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
valproate acidDrug
Also called Sodium valproate
valproate acid is a common drug which is applied for epilepsy prevention and treatment.
| Study group | Role | What they receive |
|---|---|---|
| valproate acid | Experimental | 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. Receives: Drug: valproate acid |
| placebo | Placebo comparator | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study
Secondary outcomes (3)
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.
Measured: from 0 to 42 days when the epilepsy break out
brain MRI scan
Brain MRI scan is applied to monitor the degree and progress of the brain damage.
Measured: 6 weeks after treatment
the blood concentration of VPA
the blood was collected to detect the concentration about 2 hours after the medication of VPA
Measured: On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2014 (estimated)
- Study startOct 2013
- Primary completionDec 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by Xijing HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xijing Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fei Zhou, M.D., Ph.D., Study director, Institute of Neurosurgery, Xijing Hospital, Fourth Military Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02027987
- Sponsor's protocol ID
- 20130814-7
- Acronym
- VPA
- Status last verified
- Nov 2013
- First submitted
- 28 Oct 2013
- Last updated
- 6 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study on the Neuroprotection and Epilepsy Prevention of Valproate Acid Administered After Severe Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT02027987
- Acronym / sponsor ID
- VPA / 20130814-7
- Conditions
- Traumatic Brain Injury
- Keywords
- valproate acid, traumatic brain injury, brain protection, epilepsy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Xijing HospitalUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 6 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| valproate acid | Experimental | Drug: valproate acidThe 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. |
| placebo | Placebo comparator | – |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| valproate acidAlso: Sodium valproatevalproate acid is a common drug which is applied for epilepsy prevention and treatment. | Drug | valproate acid |
Primary outcome
DRS scores
Time frame: On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study
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.
3 secondary outcomes
the time of break out and state of epilepsy
Time frame: from 0 to 42 days when the epilepsy break out
brain MRI scan
Time frame: 6 weeks after treatment
the blood concentration of VPA
Time frame: On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fei Zhou, M.D., Ph.D. study director
Institute of Neurosurgery, Xijing Hospital, Fourth Military Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing valproate acid in people with Traumatic Brain Injury, run by Xijing Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hu S Jie, M.D., Ph.D. (086-29-84773307, hushijie@fmmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DRS scores (time frame: On the 0,7th,14th,21st,28th,35th,42nd days since admitted into the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2014.