Trial Outcomes & Findings for Topiramate vs. Placebo in Preventing Weight Gain in Bipolar Disorder Treated With Olanzapine (NCT NCT00394095)
NCT ID: NCT00394095
Last Updated: 2025-04-09
Results Overview
For all participants, BMI was computed using Change in BMI \[kg/m2 (weight/height2)\] over 12 weeks from Baseline to Week 12.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
31 participants
Primary outcome timeframe
12 weeks
Results posted on
2025-04-09
Participant Flow
Thirty one bipolar adolescents with a manic or mixed episode (ages 12-18 years) were recruited from the inpatient units and outpatient clinics at the University of Cincinnati and Cincinnati Children's Hospital Medical Center.
Subjects meeting the entry criteria were randomized to treatment with topiramate or placebo in combination with olanzapine for this 12-week study.
Participant milestones
| Measure |
Experimental Group: Topiramate Group
Experimental Group Receiving oral Topiramate, 300-400mg/day for 12 weeks
|
Comparator Group: Placebo Group
Placebo Group Receiving oral placebo 300-400mg/day for 12 weeks
|
|---|---|---|
|
Screening
STARTED
|
17
|
14
|
|
Screening
COMPLETED
|
16
|
14
|
|
Screening
NOT COMPLETED
|
1
|
0
|
|
Randomized
STARTED
|
16
|
14
|
|
Randomized
COMPLETED
|
8
|
10
|
|
Randomized
NOT COMPLETED
|
8
|
4
|
Reasons for withdrawal
| Measure |
Experimental Group: Topiramate Group
Experimental Group Receiving oral Topiramate, 300-400mg/day for 12 weeks
|
Comparator Group: Placebo Group
Placebo Group Receiving oral placebo 300-400mg/day for 12 weeks
|
|---|---|---|
|
Screening
Withdrawal by Subject
|
1
|
0
|
|
Randomized
Withdrawal by Subject
|
5
|
1
|
|
Randomized
Adverse Event
|
1
|
1
|
|
Randomized
Overdose
|
1
|
0
|
|
Randomized
Lost to Follow-up
|
1
|
2
|
Baseline Characteristics
Topiramate vs. Placebo in Preventing Weight Gain in Bipolar Disorder Treated With Olanzapine
Baseline characteristics by cohort
| Measure |
Experimental Group: Topiramate Group
n=16 Participants
Experimental Group Receiving oral Topiramate, 300-400mg/day for 12 weeks
|
Comparator Group: Placebo Group
n=14 Participants
Placebo Group Receiving oral placebo 300-400mg/day for 12 weeks
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
16 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
30 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Continuous
|
14.6 years
STANDARD_DEVIATION 1.9 • n=99 Participants
|
14.0 years
STANDARD_DEVIATION 2.0 • n=107 Participants
|
14.3 years
STANDARD_DEVIATION 1.95 • n=206 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=99 Participants
|
14 participants
n=107 Participants
|
31 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: The analysis was per protocol based on change in BMI over 12 weeks in the Experimental sample (N=16) compared to the Placebo group (N=14).
For all participants, BMI was computed using Change in BMI \[kg/m2 (weight/height2)\] over 12 weeks from Baseline to Week 12.
Outcome measures
| Measure |
Experimental Group: Topiramate Group
n=16 Participants
Change in Body Weight in kilograms over 12 weeks in the Experimental Topiramate sample (N=16) compared to the Placebo group (N=14).
|
Placebo Group
n=14 Participants
Group receiving comparable dosage of placebo over 12 weeks.
|
|---|---|---|
|
Change in Body Mass Index (BMI)
|
0.8 kg/m2
Interval -0.33 to 2.33
|
1.8 kg/m2
Interval 1.2 to 11.72
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: Bipolar youth (ages 12-17) who were taking olanzapine (10-20 mg/day) for a manic episode, were given topiramate (300-400mg/day) or comparable dose placebo for 12 weeks. Analysis was per protocol.
For all participants, change in body weight in kg over 12 weeks from Baseline to Week 12.
Outcome measures
| Measure |
Experimental Group: Topiramate Group
n=16 Participants
Change in Body Weight in kilograms over 12 weeks in the Experimental Topiramate sample (N=16) compared to the Placebo group (N=14).
|
Placebo Group
n=14 Participants
Group receiving comparable dosage of placebo over 12 weeks.
|
|---|---|---|
|
Change in Body Weight
|
2.8 kg
Interval 0.85 to 14.95
|
6.4 kg
Interval 0.85 to 14.95
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Bipolar youth (ages 12-17) who took at least one dose of study medication (topiramate or placebo).
Maximum tolerated dosage of topiramate or placebo at end of study participation.
Outcome measures
| Measure |
Experimental Group: Topiramate Group
n=16 Participants
Change in Body Weight in kilograms over 12 weeks in the Experimental Topiramate sample (N=16) compared to the Placebo group (N=14).
|
Placebo Group
n=14 Participants
Group receiving comparable dosage of placebo over 12 weeks.
|
|---|---|---|
|
Tolerability of Topiramate
|
146.7 milligrams
Standard Deviation 67.4
|
175 milligrams
Standard Deviation 42.7
|
Adverse Events
Experimental Group: Topiramate Group
Serious events: 2 serious events
Other events: 15 other events
Deaths: 0 deaths
Comparator Group: Placebo Group
Serious events: 1 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Experimental Group: Topiramate Group
n=16 participants at risk
Experimental Group Receiving oral Topiramate, 300-400mg/day for 12 weeks
|
Comparator Group: Placebo Group
n=14 participants at risk
Placebo Group Receiving oral placebo 300-400mg/day for 12 weeks
|
|---|---|---|
|
Nervous system disorders
Malignant hyperthermia
|
6.2%
1/16 • Number of events 1 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
0.00%
0/14 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
|
Psychiatric disorders
Increased aggression
|
0.00%
0/16 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
7.1%
1/14 • Number of events 1 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
|
Psychiatric disorders
Suicide attempt
|
6.2%
1/16 • Number of events 1 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
0.00%
0/14 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
Other adverse events
| Measure |
Experimental Group: Topiramate Group
n=16 participants at risk
Experimental Group Receiving oral Topiramate, 300-400mg/day for 12 weeks
|
Comparator Group: Placebo Group
n=14 participants at risk
Placebo Group Receiving oral placebo 300-400mg/day for 12 weeks
|
|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal
|
37.5%
6/16 • Number of events 6 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
35.7%
5/14 • Number of events 5 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
|
Ear and labyrinth disorders
Earache
|
0.00%
0/16 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
14.3%
2/14 • Number of events 2 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
|
Musculoskeletal and connective tissue disorders
Muscle aches
|
18.8%
3/16 • Number of events 3 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
7.1%
1/14 • Number of events 1 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis
|
18.8%
3/16 • Number of events 3 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
21.4%
3/14 • Number of events 3 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
|
Skin and subcutaneous tissue disorders
Upper extremity paresthesia
|
12.5%
2/16 • Number of events 2 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
0.00%
0/14 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
|
General disorders
Headaches
|
37.5%
6/16 • Number of events 6 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
35.7%
5/14 • Number of events 5 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
|
General disorders
Chest pain
|
0.00%
0/16 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
21.4%
3/14 • Number of events 3 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
|
General disorders
Back and/or neck pain
|
18.8%
3/16 • Number of events 3 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
7.1%
1/14 • Number of events 1 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
|
Eye disorders
Ocular/visual blurriness
|
18.8%
3/16 • Number of events 3 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
7.1%
1/14 • Number of events 1 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
|
Psychiatric disorders
Worsening of mood
|
12.5%
2/16 • Number of events 2 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
7.1%
1/14 • Number of events 1 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
|
Psychiatric disorders
Sedation
|
0.00%
0/16 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
21.4%
3/14 • Number of events 3 • 12 weeks
Adverse events collected with open-ended questions and classified into categories by study team.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place