Bipolar Disorder
Conditions
Brief summary
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.
Interventions
DRUGLithium
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.
DRUGQuetiapine
Quetiapine will be started at 50 mg per day at bedtime and titrated up to 300 mg as tolerated over 1 week.
Sponsors
University Hospitals Cleveland Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Study Discontinuation | Week 16 | The time, as measured in number of days, for discontinuation due to all causes will be measured and used as the primary outcome measure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lithium vs. Quetiapine Effects on General Cardiovascular Disease Risk as Measured by Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | Screening and Week 16 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lithium Lithium: 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. | 18 |
| Quetiapine Quetiapine: Quetiapine will be started at 50 mg per day at bedtime and titrated up to 300 mg as tolerated over 1 week. | 24 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 5 |
| Overall Study | Incarcerated | 0 | 2 |
| Overall Study | Lost to Follow-up | 3 | 6 |
| Overall Study | Moved out of state | 1 | 0 |
| Overall Study | Unable to discontinue concomitant med | 1 | 0 |
| Overall Study | Unstable Medical Condition | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Lithium | Quetiapine | Total |
|---|---|---|---|
| Age, Continuous | 43.26 years STANDARD_DEVIATION 16.66 | 35.58 years STANDARD_DEVIATION 12.64 | 38.98 years STANDARD_DEVIATION 14.88 |
| Diagnosis Bipolar I Disorder | 10 participants | 15 participants | 25 participants |
| Diagnosis Bipolar II Disorder | 9 participants | 7 participants | 16 participants |
| Diagnosis Bipolar NOS | 0 participants | 2 participants | 2 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 15 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Female | 11 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Male | 7 Participants | 14 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 18 | 21 / 24 |
| serious Total, serious adverse events | 0 / 18 | 0 / 24 |
Outcome results
Primary
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
Time frame: Week 16
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lithium | Time to Study Discontinuation | 41 days |
| Quetiapine | Time to Study Discontinuation | 77 days |
Secondary
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.
Time frame: Screening and Week 16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lithium | Lithium vs. Quetiapine Effects on General Cardiovascular Disease Risk as Measured by Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | -5.5 IR Score | Standard Deviation 15.9 |
| Quetiapine | Lithium vs. Quetiapine Effects on General Cardiovascular Disease Risk as Measured by Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | 0.2 IR Score | Standard Deviation 1.6 |