Gao Bipolar Spectrum Lithium/Quetiapine Study

Study Overview
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Brief Summary
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This is a 4-month randomized open-label comparative safety, tolerability, and effectiveness trial of Lithium versus Quetiapine for subjects presenting in any phase of Bipolar who currently require a medication change for their illness. Stratified randomization will reduce bipolar type I , bipolar type II , or sub-threshold imbalance across cells. The enrollment goal is 60 subjects, over 24 months from initial regulatory approval. The primary outcome is the difference between lithium and quetiapine in the time to 'all cause' medication discontinuation.

Official Title
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Comparative Safety, Tolerability, and Effectiveness of Lithium Versus Quetiapine in Patients Across the Spectrum of Bipolar Disorder

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: Lithium
* Drug: Quetiapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide informed consent before beginning any study-specific procedures Male and female patients at least 18 years of age Meets Diagnostic and Statistical Manual -IV criteria for BPI, BP II, or National Comorbidity Survey-R criteria for sub-threshold BP with or without symptoms, in need of medication adjustment(s) Willing to be randomized to either Lithium or Quetiapine If a sexually active female of childbearing potential, be using a reliable method of contraception, such as oral contraceptive or long-term injectable or implantable hormonal contraceptive, double-barrier methods (e.g. condom and diaphragm, condom and foam, condom and sponge), intrauterine devices, and tubal ligation Women with reproductive potential must have a negative urine pregnancy test Exclusion Criteria: Unwilling to comply with study requirements Patients who have had severe adverse reaction to Lithium or Quetiapine Patients who require inpatient care Drug/alcohol dependence requiring immediate acute detoxification Pregnancy as determined by serum pregnancy test or breastfeeding History of nonresponse to Lithium at doses >900 mg ≥8 wks or to Quetiapine at doses of at least 300 mg/d ≥ 8 week for depression and at least 400-600 mg/d ≥ 4 wks for mania.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lithium<br> | Drug: Lithium<br>* Lithium will be initiated at 300 mg per day and titrated in 300 mg increments every 7days as tolerated with blood lithium levels > 0.6mEq/L.<br>* Other names: Eskalith;|
| Active Comparator: Quetiapine<br> | Drug: Quetiapine<br>* Quetiapine will be started at 50 mg per day at bedtime and titrated up to 300 mg as tolerated over 1 week.<br>* Other names: Seroquel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Study Discontinuation | The time, as measured in number of days, for discontinuation due to all causes will be measured and used as the primary outcome measure | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lithium vs. Quetiapine Effects on General Cardiovascular Disease Risk as Measured by Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | Change in homeostatic model assessment for insulin resistance (HOMA-IR) from screening to end of study. Insulin resistance is a condition in which cells fail to respond to the normal actions of the hormone in the body. The HOMA-IR is calculated using a subject's fasting plasma insulin and glucose levels. The higher the score, the higher the level of insulin resistance. | Screening and Week 16 |