Efficacy and Tolerability of Topiramate in Treatment of Bipolar Mania and Alcohol Use in Adolescents and Young Adults

Phase 4

Completed

• Conditions: Bipolar Disorder; Alcohol Abuse
• Interventions: Drug: quetiapine and placebo; Drug: Quetiapine and Topiramate

• Registration Number: NCT00550394
• Lead Sponsor: University of Cincinnati

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.

Study Timeline

• Study First Submitted: 2007-10-25
• Study First Submitted QC: 2007-10-25
• Study First Posted: 2007-10-29
• Study Start: 2008-04
• Primary Completion: 2010-06
• Study Completion: 2010-06
• Status Verified: 2014-10
• Results First Submitted: 2016-05-19
• Results First Submitted QC: 2017-04-21
• Last Update Submitted: 2017-04-21
• Results First Posted: 2017-05-23
• Last Update Posted: 2017-05-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Quetiapine and Placebo	quetiapine and placebo	Quetiapine and Placebo
Quetiapine and Topiramate	Quetiapine and Topiramate	Quetiapine and Topiramate

Primary Outcome Measures

Name	Time	Method
Drinks Per Day	baseline to 12 weeks or endpoint (up to 11 weeks)	Change in self-reported drinks/day (drinks consumed divided by the number of days during that study period).
Drinks Per Drinking Day	baseline to 12 weeks or endpoint (up to 11 weeks)	Change in drinks/drinking day (number of drinks consumed divided by the number of days during which alcohol was consumed during that study period)
Percentage of Days Abstinent	baseline to 12 weeks or endpoint (up to 11 weeks)	Change in percent days abstinent (the number of non-drinking days divided by the number of days in that study period).
Percent Heavy Drinking Days	baseline to 12 weeks or endpoint (up to 11 weeks)	Change in percent heavy drinking days (number of days of \> 4 drinks/day divided by number of days in that study period).

Trial Locations

Locations (1)

University of Cincinnati Medical Center; 🇺🇸 Cincinnati, Ohio, United States