Clinical trial NCT00550394: Efficacy and Tolerability of Topiramate in Treatment of Bipolar Mania and Alcohol Use in Adolescents and Young Adults
Official title: Quetiapine Plus Topiramate or Placebo for Bipolar Mania & Alcohol Use in Adolescents & Young Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bipolar Disorder
Alcohol Abuse
Keywords: Adolescents
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2007-10-29
Enrollment: 56
Sex: ALL
Minimum age (years): 12
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to study the effects (both good and bad) of combining quetiapine and topiramate for treating symptoms of bipolar mania (an illness with periods of elation, excessive excitement, irritability, high energy, racing thoughts, poor sleep, poor judgment, reckless behavior) and to study the effects (both good and bad) of combining quetiapine and topiramate for reducing use of alcohol.

Detailed description: Specific Aim 1: To collect preliminary data regarding the efficacy and tolerability of topiramate for the treatment of alcohol use disorders (alcohol abuse and dependence) in adolescents with bipolar disorder.

Hypothesis 1: We hypothesize that topiramate in combination with quetiapine will lead to greater reduction in alcohol consumption (number of drinks per day, number of drinks per drinking day, and number of heavy drinking days) and greater abstinence (percentage of days abstinent) compared with quetiapine alone.

Specific Aim 2: To obtain preliminary data regarding the efficacy of topiramate for reducing manic symptoms in adolescents with co-occurring alcohol use and bipolar disorders.

Hypothesis 2: We hypothesize that the topiramate in combination with quetiapine will produce greater reduction in Young Mania Rating Scale (YMRS) scores than quetiapine alone.

Eligibility criteria: Inclusion Criteria:

1. Ages 12-25 years;
2. DSM-IV-TR83 criteria for bipolar disorder, type I, manic or mixed episode;
3. Young Mania Rating Scale (YMRS)86-88 score of \> 16 at screening and baseline visits;
4. DSM-IV-TR83 criteria for current alcohol abuse or dependence;
5. Drinking \>8 drinks in 30 days within the previous 6 months while meeting DSM-IV criteria for alcohol abuse or dependence.

   One standard drink is defined as 0.35 liters of beer, 0.15 liters of wine, or 0.04 liters of 80-proof liquor;
6. Fluent in English;
7. Provision of written informed consent/assent; 8) If female and of child bearing potential, agrees to use one of the following method of birth control: complete abstinence, barrier (diaphragm or condom), or oral contraceptive containing \> 35 micrograms of ethinyl estradiol (because concomitant use of topiramate and lower estrogen oral contraceptives may lead to contraceptive failure).

Exclusion Criteria:

1. Manic symptoms resulting from acute medical illness or acute intoxication or withdrawal from drugs or alcohol as determined by medical evaluation and rapid symptom resolution;
2. Clinically significant alcohol or drug withdrawal symptoms that have the potential to cause serious consequences as determined by vital signs, the CIWA-Ar,84 and medical evaluation;
3. Any unstable medical illness or laboratory abnormalities \> 3 times upper limits of normal;
4. A documented history of mental retardation or an IQ total score \< 70 as determined by the Wechsler Abbreviated Scale of Intelligence (WASI),154 administered by a trained psychometrician;
5. Any substance use other than alcohol, nicotine, or cannabis during the 30 days prior to study participation;
6. A positive urine pregnancy test or lactating;
7. History of nephrolithiasis.
8. Treatment with concurrent mood stabilizers, antipsychotics or antidepressants;
9. Treatment with antipsychotics or other mood stabilizers within 72 hours and antidepressants within 5 days prior to randomization;
10. Treatment with fluoxetine within one month;
11. A history of non-response or hypersensitivity to quetiapine or topiramate;
12. Serious suicidal ideation (\> 3 on the CDRS-R89 suicide item, or any serious suicide attempt within the prior 60 days as judged by the investigator; 3=has thoughts about suicide or hurting themselves usually when angry);
13. Treatment for substance use during 30 days prior to screening (excluding peer support groups);
14. Court-ordered to substance use treatment;
15. Acute intoxication;
16. History of a medication change during the prior 30 days that may have precipitated manic symptoms;
17. History of a partial response (any improvement) to any existing medications as reported by treating clinician, subjects or legal guardian.

Primary outcomes:
measure: Drinks Per Day
timeFrame: baseline to 12 weeks or endpoint (up to 11 weeks)
measure: Drinks Per Drinking Day
timeFrame: baseline to 12 weeks or endpoint (up to 11 weeks)
measure: Percentage of Days Abstinent
timeFrame: baseline to 12 weeks or endpoint (up to 11 weeks)
measure: Percent Heavy Drinking Days
timeFrame: baseline to 12 weeks or endpoint (up to 11 weeks)
Secondary outcomes:
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Melissa P DelBello, MD
role: PRINCIPAL_INVESTIGATOR
References: