Official Title: “Quetiapine Plus Topiramate or Placebo for Bipolar Mania and Alcohol Use in Adolescents”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2010

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.

Intervention(s) in this Clinical Trial

• Drug: quetiapine + placebo
  • Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.
• Drug: Quetiapine + Topiramate
  • Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: 1
  • Quetiapine + Placebo
• Experimental: 2
  • Quetiapine + Topiramate

Primary Measures

• 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.
  • Time Frame: 12 weeks
    Safety Issue?: Yes

Secondary Measures

• To obtain preliminary data regarding the efficacy of topiramate for reducing manic symptoms in adolescents with co-occuring alcohol use and bipolar disorders.
  • Time Frame: 12 weeks
    Safety Issue?: No

Inclusion Criteria:

• 1. Ages 12-21 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 > 12 alcohol-containing drinks in the previous 30 days. 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 6 months 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 12 Years

Maximum Age for this Clinical Trial: 21 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Cincinnati

Overall Clinical Trial Officials and Contacts

Melissa P DelBello, MD Principal Investigator University of Cincinnati  

Overall Contact: Dana Goller, RN 513-558-4812 dana.goller@psychiatry.uc.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00550394

Study ID Number: NIAAA

ClinicalTrials.gov Identifier: NCT00550394

Health Authority: United States: Institutional Review Board