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

• Sponsor: University of Cincinnati (Other)
• Overall Status: Completed
• CT.gov ID: NCT00550394
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 56
• Location: 1
• Arms: 2
• Duration (Months): 26
• Patients Per Site Per Month: 2.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder; Alcohol Abuse	Drug: quetiapine and placebo; Drug: Quetiapine and Topiramate	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Quetiapine Plus Topiramate or Placebo for Bipolar Mania & Alcohol Use in Adolescents & Young Adults
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Quetiapine and Placebo Quetiapine and Placebo	Drug: quetiapine and 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.; Other Names: Quetiapine
Experimental: Quetiapine and Topiramate Quetiapine and Topiramate	Drug: Quetiapine and 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.; Other Names: Topiramate

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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)

3. 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).

4. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 25 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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;

1. Fluent in English;

2. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45227

Sponsors and Collaborators

• University of Cincinnati
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Melissa P DelBello, MD, University of Cincinnati

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Melissa Delbello, Professor, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT00550394
• Other Study ID Numbers: NIAAA; R21AA016372
• First Posted: Oct 29, 2007
• Last Update Posted: May 23, 2017
• Last Verified: Oct 1, 2014

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Melissa Delbello, Professor, University of Cincinnati: Adolescents
• Additional relevant MeSH terms: Alcoholism; Bipolar Disorder; Topiramate; Quetiapine Fumarate

Study Results

Participant Flow

Recruitment Details	56 study participants were consented for study participation, of which 17 were screen fails.
Pre-assignment Detail	56 study participants were consented for study participation, of which 17 were screen fails.

Arm/Group Title	Quetiapine and Placebo	Quetiapine and Topiramate
Arm/Group Description	Quetiapine and Placebo quetiapine and 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.	Quetiapine and Topiramate Quetiapine and 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.
Period Title: Overall Study
STARTED	21	18
COMPLETED	9	5
NOT COMPLETED	12	13

Baseline Characteristics

Arm/Group Title	Quitiapine and Placebo	Quitiapine andTopiramate	Total
Arm/Group Description	Quetiapine and Placebo quetiapine and 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.	Quetiapine and Topiramate Quetiapine andTopiramate: 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.	Total of all reporting groups
Overall Participants	21	18	39
Age (Count of Participants)
<=18 years	21 100%	18 100%	39 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	18 (3.1)	17.7 (2.4)	17.9 (2.7)
Sex: Female, Male (Count of Participants)
Female	16 76.2%	8 44.4%	24 61.5%
Male	5 23.8%	10 55.6%	15 38.5%
Region of Enrollment (participants) [Number]
United States	21 100%	18 100%	39 100%

Outcome Measures

1. Primary Outcome

Title	Drinks Per Day
Description	Change in self-reported drinks/day (drinks consumed divided by the number of days during that study period).
Time Frame	baseline to 12 weeks or endpoint (up to 11 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine + Placebo	Quetiapine + Topiramate
Arm/Group Description	Quetiapine + Placebo 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.	Quetiapine + Topiramate 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.
Measure Participants	21	18
Mean (Standard Deviation) [Drinks per day]	-1.4 (2.3)	-2.4 (5.1)

2. Primary Outcome

Title	Drinks Per Drinking Day
Description	Change in drinks/drinking day (number of drinks consumed divided by the number of days during which alcohol was consumed during that study period)
Time Frame	baseline to 12 weeks or endpoint (up to 11 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine and Placebo	Quetiapine and Topiramate
Arm/Group Description	Quetiapine and Placebo	Quetiapine and Topiramate
Measure Participants	21	18
Mean (Standard Deviation) [Drinks per drinking day]	-7.2 (10.2)	-7.3 (6.0)

3. Primary Outcome

Title	Percentage of Days Abstinent
Description	Change in percent days abstinent (the number of non-drinking days divided by the number of days in that study period).
Time Frame	baseline to 12 weeks or endpoint (up to 11 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine and Placebo	Quetiapine and Topiramate
Arm/Group Description	Quetiapine and Placebo	Quetiapine and Topiramate
Measure Participants	21	18
Mean (Standard Deviation) [Percentage of days abstinent]	15 (19)	14 (23)

4. Primary Outcome

Title	Percent Heavy Drinking Days
Description	Change in percent heavy drinking days (number of days of > 4 drinks/day divided by number of days in that study period).
Time Frame	baseline to 12 weeks or endpoint (up to 11 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine and Placebo	Quetiapine and Topiramate
Arm/Group Description	Quetiapine and Placebo	Quetiapine and Topiramate
Measure Participants	21	18
Mean (Standard Deviation) [Percent heavy drinking days]	-10 (19)	-14 (25)

Adverse Events

Time Frame	3 years 9 months
Arm/Group Title	Quetiapine and Placebo		Quetiapine and Topiramate
Arm/Group Description	Quetiapine and Placebo 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.		Quetiapine and Topiramate 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.
All Cause Mortality
	Quetiapine and Placebo		Quetiapine and Topiramate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Quetiapine and Placebo		Quetiapine and Topiramate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/21 (38.1%)		2/18 (11.1%)
General disorders
Suicidal ideation	7/21 (33.3%)		2/18 (11.1%)
Suicide Attempt	1/21 (4.8%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Quetiapine and Placebo		Quetiapine and Topiramate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/21 (19%)		11/18 (61.1%)
General disorders
sedation	4/21 (19%)		11/18 (61.1%)
Difficulty Arousing	3/21 (14.3%)		9/18 (50%)

Limitations/Caveats

Additional studies are needed as topiramate has not been systematically assessed. This study was to collect pilot data and more data will need to be collected.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.