Pioglitazone for the Treatment of Bipolar Disorder and Comorbid Metabolic Syndrome or Insulin Resistance

Study Overview
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Brief Summary
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The study is an open-label 8-week adjunctive trial of pioglitazone for the acute relief of bipolar depression comorbid with metabolic syndrome/insulin resistance. Subjects who experience a partial or full response will have the option of continuing in an acute continuation phase lasting up to 12 weeks. The extension phase will allow assessment of the safety and tolerability of pioglitazone during the acute continuation period.

Official Title
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Pioglitazone for the Treatment of Bipolar Disorder and Comorbid Metabolic Syndrome or Insulin Resistance

Conditions
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Metabolic Syndrome, Bipolar Depression, Insulin Resistance

Intervention / Treatment
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* Drug: Pioglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be male or female between the ages of 18 and 70 Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnosis of bipolar disorder (type I, II, or NOS) Currently depressed as confirmed by the MINI-Plus at the screening visit Currently receiving treatment with an anti-manic drug Meets criteria for metabolic syndrome or insulin resistance Exclusion Criteria: Pregnancy or breast feeding Unstable or inadequately treated medical illness as judged by the investigator Severe personality disorder Serious suicidal risk 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 an antidiabetic/glucose-lowering agent. 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) Fasting blood glucose >150 mg/dL Hb A1c > 7.5%

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pioglitazone<br>Pioglitazone has been approved by the U.S. Food and Drug Administration (FDA) to help people who are diagnosed with diabetes | Drug: Pioglitazone<br>* An open-label 12-week trial of pioglitazone monotherapy. The investigators will titrate pioglitazone to the maximum tolerable dose up to 45mg per day.<br>* Other names: Actos;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Inventory of Depressive Symptomatology-Clinician Rated (IDS-CR) Score | Inventory of Depressive Symptoms-Clinician rated, 30 item (IDS-C30) score change from baseline to study endpoint. IDS-C30 total scores can range from 0 to 84, with higher scores indicating a worse outcome | Week 0 - Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR16) Total Score | The QIDS-SR16 is a 16-item, self report assessment. Total scores can range from 0 to 27, with higher scores indicating a worse outcome | Week 0 - Week 8 | 
| Response Rates on the IDS-CR, Montgomery Asberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) | A participant is considered to have responded if their total score on either the MADRS or QIDS-SR16 decreases by at least 50% between their Week 0 visit and Week 8 visit. | Week 0 - Week 8 | 
| Remission Rates Based on IDS-CR, QIDS-SR, and MADRS Scores | A participant is considered in remission if their total score on the MADRS is > 7, their total score on the QIDS-SR16 > 6 and/or their total score on the IDS-CR is > 12 at Week 8. | Week 0 - Week 8 | 
| Change in Clinical Global Impressions-Bipolar Version (CGI-BP) | The CGI-BP asks the clinician one question: Considering your total clinical experience with this particular population, how mentally ill is the patient at this time? which is rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. | Week 0 - Week 8 |