Valproate for Mood Swings and Alcohol Use Following Head Injury

NCT01760785 | Completed Results DMC

• 2 other identifiers: 08-0582PT075168
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Successful treatment of traumatic brain injury (TBI)-induced mood lability may reduce or eliminate drinking behaviors in persons with alcohol abuse/dependence (AA/D) and affective lability following TBI. Observed clinically, the symptoms of poorly regulated affective expression of AA/D+TBI patients who reach alcohol abstinence do not appear to be those of an idiopathic mood or anxiety disorder. These symptoms do not present the severity or the same natural courses as do Major Depressive Disorder, Bipolar Illness, or Anxiety Disorder, for example. Instead, both symptoms and course appear more characteristic of the sustained affect lability often observed following TBI. This observation suggests that TBI survivors represent a patient group for whom treatment of neuropsychiatric symptoms following TBI may alleviate both TBI-related affect lability and also heavy ethanol use by treating the condition that is contextually related to excessive alcohol use. Based on this concept of consequently treating AA/D through the management of post-TBI affective lability, this study was conducted observing the efficacy of divalproex sodium on the severity of affective lability and AA/D in persons suffering from a moderate TBI. Divalproex sodium has been shown to ameliorate mood disorders, even in those with substance abuse problems. This drug has also shown positive results as an alternate medication to benzodiazapines in the treatment of alcohol withdrawal, significantly reducing the progression of withdrawal symptoms in patients.

Conditions

Traumatic Brain Injury (TBI); Alcoholism

Keywords

Veterans; Traumatic Brain Injury(TBI); Alcoholism

Outcome Measures

Primary Outcomes (1)

• Severity of Affective Lability Based on Shortened Agitated Behavior Scale

  Severity of affective lability was measured using a shortened version of the Agitated Behavior Scale (ABS). The ABS is used to assess the nature and extent of present agitation. Eight items from the 14-item scale were used, which measured the presence and severity of various affective lability symptoms including: short attention span, impulsivity, uncooperative behavior, violent tendencies, restlessness, rapid or excessive talking, sudden changes in mood, and easily initiated or excessive crying and/or laughter. Each of the eight items was scored using a 1-4 Likert scale, where 1 stands for absence of symptom and 4 stands for presence to an extreme degree. The minimum possible score for this measure was 8, and the maximum possible score was 32. Due to the nature of the measure, a lower score indicated less severe affective lability, while conversely higher scores indicated more severe affective lability. The mean of scores for weeks 2 through 8 for each group were reported.

  Weeks 2 through 8

Secondary Outcomes (1)

• Frequency of Alcohol Use

  Weeks 1-10

Study Arms (2)

divalproex sodium

ACTIVE COMPARATOR

Drug: divalproex sodium

sugar pill

PLACEBO COMPARATOR

Drug: Placebo

Interventions

divalproex sodium DRUG

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.

divalproex sodium

Placebo DRUG

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.

Also known as: sugar pill

sugar pill

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• United States Department of Defense: collaborator

Study Sites (1)

Denver Veteran's Affairs Medical Center

Denver, Colorado, 80220, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic; Alcoholism

Interventions

Valproic Acid; Sugars

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Carbohydrates

Results Point of Contact

• Title: Dr. Thomas Beresford
• Organization: Denver Research Institute

thomas.beresford@ucdenver.edu

303-399-8020

Study Officials

• Thomas P Beresford, MD

  Denver Veteran's Affairs Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2012
• First Posted: January 4, 2013
• Study Start: September 1, 2008
• Primary Completion: August 1, 2014
• Study Completion: June 1, 2016
• Last Updated: January 10, 2020
• Results First Posted: June 15, 2016

Record last verified: 2020-01

Locations

US (1)