Bipolar Disorder, Weight Gain
Conditions
Keywords
Bipolar Disorder, Weight Gain
Brief summary
The primary objective of this study is to examine the efficacy of topiramate in combination with olanzapine for the prevention of weight gain in youth with bipolar disorder. The secondary objective is to examine the tolerability of topiramate in combination with olanzapine for the prevention of weight gain in youth with bipolar disorder.
Detailed description
After consent and screening, patients will be initiated on 5mg or 10mg per day of olanzapine. Olanzapine doses will be titrated to 10-20 mg of olanzapine over one week, to a maximum of 20mg by day 21. Patients will also receive either topiramate (25mg bid titrated over 18 days to 150 mg bid. with flexibility to titrate to 200mg bid) or matched placebo. Topiramate will be initiated at a dose of 25 mg bid and will be increased by 25 mg bid every three days as tolerated. Patients will be evaluated by a blinded (to treatment status and adverse events) rater.
Interventions
DRUGTopiramate
Oral topiramate 300-400mg/day for 12 weeks
DRUGPlacebo
Matched placebo to Experimental arm
Sponsors
Eli Lilly and Company
University of Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients, ages 10-18 years. 2. Female patients of menarche must be using a medically accepted means of contraception (e.g. oral contraceptives, Depo-Provera, abstinence). 3. Each patient's authorized legal guardian must understand the nature of the study and must provide written informed consent. Each patient must also give assent to study participation. 4. Patients must have a diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) bipolar disorder, type I and currently display an acute manic or mixed episode as determined by K-SADS (Geller et al 2000). 5. Patients must have a baseline (day 0) Young Mania Rating Scale score of at least 16. 6. Subjects should be fluent in English.
Exclusion criteria
1. Female patients who are either pregnant or lactating. 2. Clinically significant or unstable hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, hematologic or other systemic medical conditions. 3. Any history of current or past diabetes that has been treated with pharmacological intervention. 4. Neurological disorders including epilepsy, stroke, or severe head trauma. 5. Clinically significant laboratory abnormalities (\> 3 times upper limit of normal), on any of the following tests: CBC with differential, electrolytes, BUN, creatinine, hepatic transaminases, lipid profile, fasting glucose, urinalysis, or thyroid indices. Clinically abnormal ECG. 6. Manic or mixed episode due to a general medical condition or substance-induced mania (DSM-IV-TR). 7. Mental retardation (IQ \<70). 8. History of hypersensitivity to or intolerance of olanzapine or topiramate. 9. Prior history of olanzapine or topiramate non-response or allergic reaction. 10. DSM-IV substance (except nicotine or caffeine) dependence within the past 3 months. 11. Judged clinically to be at suicidal risk (defined as having active suicidal ideation, intent or plan, or a serious suicide attempt within 30 days, or a baseline Children's Depression Rating Scale suicide score of \>3). 12. Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections and day 0. 13. Treatment with concurrent mood stabilizers or anticonvulsants, benzodiazepines (except as described below), psychostimulants, guanethidine, or guanadrel, or antidepressants. 14. Schizophrenia or other psychotic disorders (including schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, shared psychotic disorder, psychotic disorder due to a general medical condition, substance-induced psychotic disorder, psychotic disorder not otherwise specified) as defined in the DSM-IV. 15. Major depressive disorder, dysthymic disorder, depressive disorder not otherwise specified.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Mass Index (BMI) | 12 weeks | For all participants, BMI was computed using Change in BMI \[kg/m2 (weight/height2)\] over 12 weeks from Baseline to Week 12. |
| Change in Body Weight | 12 weeks | For all participants, change in body weight in kg over 12 weeks from Baseline to Week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability of Topiramate | 12 weeks | Maximum tolerated dosage of topiramate or placebo at end of study participation. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
Subjects meeting the entry criteria were randomized to treatment with topiramate or placebo in combination with olanzapine for this 12-week study.
Participants by arm
| Arm | Count |
|---|---|
| Experimental Group: Topiramate Group Experimental Group Receiving oral Topiramate, 300-400mg/day for 12 weeks | 16 |
| Comparator Group: Placebo Group Placebo Group Receiving oral placebo 300-400mg/day for 12 weeks | 14 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomized | Adverse Event | 1 | 1 |
| Randomized | Lost to Follow-up | 1 | 2 |
| Randomized | Overdose | 1 | 0 |
| Randomized | Withdrawal by Subject | 5 | 1 |
| Screening | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Comparator Group: Placebo Group | Experimental Group: Topiramate Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 14 Participants | 16 Participants | 30 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 14.0 years STANDARD_DEVIATION 2 | 14.6 years STANDARD_DEVIATION 1.9 | 14.3 years STANDARD_DEVIATION 1.95 |
| Region of Enrollment United States | 14 participants | 16 participants | 31 participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 14 |
| other Total, other adverse events | 15 / 16 | 13 / 14 |
| serious Total, serious adverse events | 2 / 16 | 1 / 14 |
Outcome results
Primary
Change in Body Mass Index (BMI)
For all participants, BMI was computed using Change in BMI \[kg/m2 (weight/height2)\] over 12 weeks from Baseline to Week 12.
Time frame: 12 weeks
Population: 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).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Experimental Group: Topiramate Group | Change in Body Mass Index (BMI) | 0.8 kg/m2 |
| Placebo Group | Change in Body Mass Index (BMI) | 1.8 kg/m2 |
Primary
Change in Body Weight
For all participants, change in body weight in kg over 12 weeks from Baseline to Week 12.
Time frame: 12 weeks
Population: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Experimental Group: Topiramate Group | Change in Body Weight | 2.8 kg |
| Placebo Group | Change in Body Weight | 6.4 kg |
Secondary
Tolerability of Topiramate
Maximum tolerated dosage of topiramate or placebo at end of study participation.
Time frame: 12 weeks
Population: Bipolar youth (ages 12-17) who took at least one dose of study medication (topiramate or placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental Group: Topiramate Group | Tolerability of Topiramate | 146.7 milligrams | Standard Deviation 67.4 |
| Placebo Group | Tolerability of Topiramate | 175 milligrams | Standard Deviation 42.7 |