Bipolar Disorder, Insulin Resistance
Conditions
Keywords
Bipolar Disorder, Insulin Resistance
Brief summary
The primary objective is to test the hypothesis that adjunctive pioglitazone is more effective than placebo for the relief of acute depressive symptoms resulting from bipolar disorder. The secondary objectives are to determine potential moderators and mediators of antidepressant efficacy.
Detailed description
The study is a double-blind, placebo-controlled 8-week trial of pioglitazone, either as monotherapy or adjunctive to a mood stabilizer, for the acute relief of bipolar depression. The enrollment goal is 80 subjects (40 patients each in the pioglitazone treatment group and the placebo treatment group). Screening Phase: Patients who have been prescribed a mood stabilizer for \> 4 weeks and are on a therapeutic dose will proceed directly to the Screening Visit. For situations in which the patient prefers to be taking a mood stabilizer or where the treating psychiatrist feels it is clinically necessary, a mood stabilizer (lithium, divalproex, carbamazepine, lamotrigine, olanzapine, quetiapine, risperidone, aripiprazole, ziprasidone or lurasidone) will be initiated (see Mood Stabilizer Initiation section below). For this set of patients who do begin a mood stabilizer, the Screening Phase may last up to 8 weeks. Otherwise, subjects who do not come in on a mood stabilizer will proceed directly to screening. Double-Blind, Placebo-Controlled Study Period (Week 1 to Week 8): Patients who meet inclusion/exclusion criteria will be randomized to study treatment at the baseline/randomization visit within 30 days of the screening visit. The efficacy and safety assessments will be carried out at baseline/randomization and then weekly or every two weeks for a total of 8 weeks.
Interventions
DRUGPioglitazone
Pioglitazone will be initiated at a starting daily dose of 15 mg. After 7 days, the dose may be increased to 30 mg and after 35 days may be increased to a maximum of 45 mg per day.
DRUGPlacebo
Placebo will be initiated at a starting daily dose of 15 mg. After 7 days, the dose may be increased to 30 mg and after 35 days may be increased to a maximum of 45 mg per day.
Sponsors
The Depressive and Bipolar Disorder Alternative Treatment Foundation
University Hospitals Cleveland Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be male or female \>= 18 years of age * Diagnostic and Statistical Manual-IV (DSM-IV) diagnosis of bipolar disorder (type I, II, or NOS) * Currently depressed as confirmed by the Mini-International Neuropsychiatric Interview (M.I.N.I.)-Plus at the screening visit * Inventory of Depressive Symptoms total score \> 25 or Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16) \> 11 at study baseline * Women of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study. Acceptable methods of contraception include barrier method with spermicide, abstinence, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
Exclusion criteria
* Pregnant or breast feeding * Unstable or inadequately treated medical illness as judged by the investigator * Severe personality disorder * Serious suicidal risk as judged by the investigator or having a score ≥ 4 on Montgomery Asberg Depression Rating Scale (MADRS) item number 10 (suicidal thoughts) at screening or baseline * Known history of intolerance or hypersensitivity to pioglitazone * Treatment with pioglitazone in the 3 months prior to randomization * Dependence on alcohol or drugs (other than nicotine) in the 3 months prior to study entry * Currently taking insulin or rosiglitazone. * Diagnosed with dementia * Acute Mania as defined by a Young Mania Rating Scale (YMRS) score \> 15 * Diagnosed with heart failure * Transaminase elevation \>2.5 times the upper limit of normal * Presence of renal impairment (eg. creatinine \> 1.5) * History of bladder carcinoma * Fasting blood glucose \>150 mg/dL and Hb A1c\> 7%; participants meeting these criteria will be referred to an endocrinologist or their primary care physician for a diabetes evaluation and education. * Receiving acute series of electroconvulsive therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score | Baseline and Week 8 | Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) is designed to assess the severity of depressive symptoms. Total scores can range from 0 to 84 with higher scores indicating a higher severity of depressive symptoms |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone Pioglitazone: Pioglitazone will be initiated at a starting daily dose of 15 mg. After 7 days, the dose may be increased to 30 mg and after 35 days may be increased to a maximum of 45 mg per day. | 17 |
| Placebo Placebo: Placebo will be initiated at a starting daily dose of 15 mg. After 7 days, the dose may be increased to 30 mg and after 35 days may be increased to a maximum of 45 mg per day. | 20 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | New Substance Use Disorder | 1 | 0 |
| Overall Study | Required Medication Change | 0 | 1 |
Baseline characteristics
| Characteristic | Pioglitazone | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 46.71 years STANDARD_DEVIATION 12.071 | 43.65 years STANDARD_DEVIATION 12.979 | 45.05 years STANDARD_DEVIATION 12.492 |
| Bipolar Diagnosis BP 1 | 11 Participants | 13 Participants | 24 Participants |
| Bipolar Diagnosis BP 2 | 5 Participants | 7 Participants | 12 Participants |
| Bipolar Diagnosis BP NOS | 1 Participants | 0 Participants | 1 Participants |
| Gender Female | 10 Participants | 14 Participants | 24 Participants |
| Gender Male | 7 Participants | 6 Participants | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 6 Participants | 12 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 | 11 Participants | 14 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 17 | 8 / 20 |
| serious Total, serious adverse events | 0 / 17 | 0 / 20 |
Outcome results
Primary
Change in Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score
Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) is designed to assess the severity of depressive symptoms. Total scores can range from 0 to 84 with higher scores indicating a higher severity of depressive symptoms
Time frame: Baseline and Week 8
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone | Change in Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score | 31.4 units on a scale | Standard Error 3 |
| Placebo | Change in Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score | 24.3 units on a scale | Standard Error 2.7 |