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

Phase 4

Completed

Brief Summary: 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.

Recruitment & Eligibility

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%

Arm && Interventions

Group	Intervention	Description
Pioglitazone	Pioglitazone	Pioglitazone has been approved by the U.S. Food and Drug Administration (FDA) to help people who are diagnosed with diabetes

Primary Outcome Measures

Name	Time	Method
Change in the Inventory of Depressive Symptomatology-Clinician Rated (IDS-CR) Score	Week 0 - Week 8	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

Secondary Outcome Measures

Name	Time	Method
Change in Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR16) Total Score	Week 0 - Week 8	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
Response Rates on the IDS-CR, Montgomery Asberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR)	Week 0 - Week 8	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.
Remission Rates Based on IDS-CR, QIDS-SR, and MADRS Scores	Week 0 - Week 8	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.
Change in Clinical Global Impressions-Bipolar Version (CGI-BP)	Week 0 - Week 8	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.