Pioglitazone for the Treatment of Bipolar Depression

NCT ID: NCT01717040

Last Updated: 2017-01-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2016-03-31

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.

Conditions

Bipolar Disorder; Insulin Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Pioglitazone

Group Type: EXPERIMENTAL

Pioglitazone

Intervention Type: DRUG

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.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Actos; Sugar Pill

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Depressive and Bipolar Disorder Alternative Treatment Foundation

OTHER

Sponsor Role: collaborator

University Hospitals Cleveland Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Joseph Calabrese, MD

Director, Mood Disorders Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David Kemp, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Cleveland Medical Center

Locations

University Hospitals Cleveland Medical Center - Mood Disorders Program

Cleveland, Ohio, United States

Countries

United States

References

Aftab A, Kemp DE, Ganocy SJ, Schinagle M, Conroy C, Brownrigg B, D'Arcangelo N, Goto T, Woods N, Serrano MB, Han H, Calabrese JR, Gao K. Double-blind, placebo-controlled trial of pioglitazone for bipolar depression. J Affect Disord. 2019 Feb 15;245:957-964. doi: 10.1016/j.jad.2018.11.090. Epub 2018 Nov 13.

Reference Type: DERIVED

PMID: 30699881 (View on PubMed)

Other Identifiers

Kemp DBDAT

Identifier Type: -

Identifier Source: org_study_id