This trial is active, not recruiting.

Conditions traumatic brain injury (tbi), alcoholism
Treatments divalproex sodium, placebo
Sponsor University of Colorado, Denver
Collaborator United States Department of Defense
Start date September 2008
End date August 2014
Trial size 50 participants
Trial identifier NCT01760785, 08-0582, PT075168


Despite the body's natural healing during the first year after a head injury, many veterans who have suffered even mild brain injuries find themselves easily upset or fearful as they go about their daily lives. While these reactions to the world around them were easily managed before the head injury, they now occur with little or no interruption and are exceedingly difficult to manage. Such reactions include a sense of always being upset or fearful that often makes it difficult to get along with family members, friends, coworkers, and employers. This may lead to broken marriages, unemployment, and even homelessness.

Some people with head injuries try to manage their unmanageable moods by drinking alcohol because it can create a sense of calm. However, alcohol's actions are short in duration. Most find that they have to drink more and more for a similar calming effect, and they soon become dependent on alcohol. This makes working and being part of their families even more difficult.

To treat the unmanageable mood, we tried a medicine called valproate, one that eases mood problems in people without head injury. We gave valproate to head injured persons with mood problems in a "non-blinded" study where both the doctor and the patient knew that the medicine was valproate and both were optimistic that it would work. In a small sample of eighteen people, 85% found mood relief and most of those either stopped drinking alcohol or drank much less than before. However, this might have been because both the doctor and patient were hopeful that the medication would make the patient feel better or because the medicine actually worked.

The only way to know for sure if the medicine works is to perform a study in which people receive either valproate or a sugar pill while neither they nor their doctor know which one they are taking. This is called a double blind study, as proposed here, and will involve nearly three times as many head injured persons as the first study.

If it is successful, the new study will show that valproate treatment helps head injured people manage their moods and allows them to return to families, friends, and work. It will also show that they drink alcohol less or not at all, improving their health even further. Then doctors will know that they can use this medicine for large numbers of people who suffer from head injury and help them to lead normal lives. If the outcome of the study shows that the medicine works well, doctors can then use this medicine to treat people with head injury immediately after the study results are published.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
(Active Comparator)
divalproex sodium
Doses will be given in 250mg increments and titrated over the first four days of study until a starting dose of 750 mg is reached. The Study Oversight Team, who is not involved in any clinical visits, will be un-blinded to study drug assignment and will have plasma concentration results and adverse event reports available to them. If a subject has no adverse events and is not at therapeutic level as indicated by the blood levels, the Study Oversight Team may inform the research pharmacy to increase the dose by 1 tablet of 250 mg to 1000 mg per day. The Study Oversight Team may also inform the research pharmacy to reduce the daily dosage back down to 750 mg per day if plasma concentrations or adverse events become intolerable. The maximum dose for the purpose of this study will be 1250 mg daily and the minimum dose will be 750 mg daily. Subjects who cannot tolerate the minimum dose will be excluded from any further study participation.
(Placebo Comparator)
placebo sugar pill
Doses will be titrated over the first four days of study in the same manner as the active study drug. After titration, the research pharmacy may increase the dose by 1 tablet per day, in the same fashion that the active drug may be adjusted, so that the participant and clinical team remain blinded to the drug assignment. The research pharmacy may also reduce the daily dosage back down by one tablet per day for the same reason.

Primary Outcomes

Affective Lability
time frame: Weeks 1-10

Secondary Outcomes

Alcohol Use
time frame: Weeks 1-10

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

Inclusion Criteria: - Veteran - history of closed-head traumatic brain injury (TBI) at least one year prior to enrollment - symptoms of affective lability such as mood swings, irritability, frustration and anxiety - currently using alcohol Exclusion Criteria: - history of Axis I bipolar disorder or anxiety disorder prior to the TBI - skull opened either surgically or traumatically - history of stroke - current diagnosis or past history of major psychosis as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) - active liver disease - evidence of the alcohol amnesic syndrome - history of seizure disorder other than those caused by ethanol withdrawal - any type of dementia - current suicidal/homicidal ideations - symptomatic thiamine, folate or Vitamin B-12 deficiency - HIV positive - any medical conditions that would constitute contraindications to treatment with divalproex sodium

Additional Information

Official title A Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury
Principal investigator Thomas P Beresford, MD
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by University of Colorado, Denver.