- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01559857
Pioglitazone in Patients With Mood Disorders
Pioglitazone Treatment for Insulin Resistant Patients With Mood Disorders
The purpose of this study is to see how an insulin sensitizing medication, Pioglitazone, can cause changes in mood in some depressed patients. Study participants receive assessment of their cognitive and metabolic functioning.
If they meet criteria, they will be asked to take either Pioglitazone or a placebo for a 90-day trial. Participants will undergo an Oral Glucose Tolerance Test to measure fasting insulin and glucose levels, as well as routine blood testing.
The investigators hope to quantify the role of Pioglitazone in patients with mood disorders and compare the values to those previously obtained in a healthy age-matched control population. The investigators also hope to examine the association between IR and cognitive performance and clinical course of depression in patients with mood disorders.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
While the association between insulin resistance (IR) and depressive symptoms is well documented (Gold et al., 2005), causal aspects of the relationship are incompletely documented and likely bidirectional. As the current prevalence rates of DM2 and related diseases grow worldwide and its associated metabolic consequences become more salient, it is increasingly critical to understand the role of IR in depressive disorders.
Insulin has been shown to alter central nervous system (CNS) concentrations of neurotransmitters such as dopamine (Lozovsky et al., 1981) and norepinephrine (Boyd et al., 1985), by a variety of mechanisms, as well as to have direct electrophysiological effects on neuronal activity (Boyd et al., 1985). Additionally, induced IR in the CNS has been shown to result in cognitive and behavioral alterations in animal models (Kovacs and Hajnal, 2009).
Accordingly, when depression manifests as a sequela of metabolic disorders such as obesity and DM2, it is hypothesized to be associated with resistance of CNS structures to the effects of insulin, which may derive from genetic polymorphisms, as well as from long-term exposure to excess amounts of circulating insulin due to peripheral IR (Okamura et al., 2000b). Thus, "overcoming" central IR," for example by pharmacological interventions, could be an attractive strategy in the treatment and prevention of these disorders.
This study aimed to assess mood effects in a 12-week double-blind, randomized-controlled trial of adjuvant treatment with the PPARγ-agonist pioglitazone, an insulin-sensitizing agent, compared with treatment with placebo, in participants with non-psychotic, non-remitting depression receiving standard psychiatric regimens for unipolar or bipolar depression. Pioglitazone is an FDA-approved, insulin-sensitizing treatment for DM2 and has particularly beneficial effects on lipid profile (Goldberg et al., 2005) and rate of cardiovascular events (Lincoff et al., 2007) in this population. Furthermore, in assessing the utility of an additive insulin-sensitizing agent on mood outcomes in both insulin sensitive and insulin resistant patients, this study attempted to disentangle the role of insulin-sensitizing and anti-inflammatory mechanisms.
In an a prior manner, this study's aims were twofold: (1) to assess whether treatment with pioglitazone would result in significantly greater mood improvement compared to treatment with placebo among patients with unremitted depression despite treatment as usual (TAU) and (2) to examine mechanisms of proposed effects of a PPARγ-agonist on mood outcomes by comparing treatment outcomes based on surrogate markers of glucose metabolic status (hereafter referred to IR and IS) between IR and insulin sensitive (IS) participants.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
California
-
Palo Alto, California, United States, 94305
- Stanford University Department of Psychiatry & Behavioral Sciences
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age between 20 and 65 years
- BMI between 25 and 35
- Diagnosis of unipolar, non-psychotic, non-melancholic major depressive disorder (MDD) or depressive episode of bipolar disorder (Bipolar I, II or NOS)
- Depression severity as defined by score of < 12 on the 21-item Hamilton Rating Scale for Depression and no psychiatric admission within 6 months from study entry and no suicide attempt within the last 12 months
- Willingness to sign human subjects consent form
Exclusion Criteria:
- Diagnosis of possible or probable cognitive impairment
- For women only: pregnancy, breastfeeding
- Personal history of Type I or Type II diabetes
- Unstable cardiovascular disease or other major medical condition, or history of myocardial infarction within the previous year
- Significant cerebrovascular disease, as evidenced by neurological examination, uncontrolled hypertension (systolic blood pressure > 170 or diastolic blood pressures > 100)
- Current drug or alcohol abuse
- History of neurological disorder, e.g. multiple sclerosis, stroke etc
- Use of any drug that may significantly affect psychometric testing or the insulin testing
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Pioglitazone
50% of participants will be allocated to 12 weeks of treatment with 30 mg/day of Pioglitazone.
|
30mg once daily for 12 weeks
Other Names:
|
Placebo Comparator: Sugar pill
50% of participants will be randomized to 12 weeks of treatment with placebo pill.
|
Placebo
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hamilton Depression Rating Scale at Baseline
Time Frame: Baseline
|
The HDRS-21 was used to screen for unremitted depression.
The HDRS-21 is scored on a scale from 0 to 21, where 0 is the lowest level of depression severity and 21 is the highest level of depression severity.
Unremitted depression is characterized by a score of ≥7.
The HDRS-21 scores at baseline are shown in the data table below.
|
Baseline
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Fasting Insulin Measurements at Baseline
Time Frame: Baseline
|
The fasting plasma insulin measurements taken at baseline are shown in the data table below.
|
Baseline
|
Change in HDRS-21: From Baseline to 12 Weeks
Time Frame: 12 weeks
|
The HDRS-21 was administered at baseline and at the end of 12 weeks, and the mean difference between the two time points was calculated.
The HDRS-21 is scored on a scale from 0 to 21, where 0 is the lowest level of depression severity and 21 is the highest level of depression severity.
|
12 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Natalie Rasgon, MD, PhD, Stanford University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- R21MH093948-01A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Insulin Resistance
-
Washington University School of MedicineNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National...CompletedEndoplasmic Reticulum Stress | HIV Related Insulin Resistance | Protease Inhibitor Related Insulin ResistanceUnited States
-
Paloma Almeda-ValdésCompleted
-
German Diabetes CenterYale UniversityRecruiting
-
National Institute of Diabetes and Digestive and...Active, not recruitingSevere Insulin ResistanceUnited States
-
Eunice Kennedy Shriver National Institute of Child...Completed
-
Assiut UniversityCompleted
-
National Taiwan UniversityNational Cheng-Kung University HospitalCompletedExercise, Insulin Resistance, Visceral Adipose TissueTaiwan
-
The University of Texas Medical Branch, GalvestonCompletedInsulin Resistance, DiabetesUnited States
-
University Health Network, TorontoCompletedInsulin Resistance, DiabetesCanada
-
University Health Network, TorontoCompletedInsulin Resistance Syndrome X | Pancreatic Beta Cell FunctionCanada
Clinical Trials on Sugar Pill
-
Massachusetts General HospitalGaneden Biotech, Inc.TerminatedIrritable Bowel Syndrome | Major Depressive DisorderUnited States
-
Harvard University Faculty of MedicineBeth Israel Deaconess Medical CenterCompletedIrritable Bowel SyndromeUnited States
-
Hospital de Clinicas de Porto AlegreCoordenação de Aperfeiçoamento de Pessoal de Nível Superior.; Conselho Nacional... and other collaboratorsCompletedPeriampullary Carcinoma NosBrazil
-
GlaxoSmithKlineCompletedHealthy Subjects | Infections, BacterialAustralia
-
USDA Grand Forks Human Nutrition Research CenterCompletedInsomnia | Nutritional DeficiencyUnited States
-
Neurotune AGCross Research S.A.; Triclinium clinical trial project managment LTDCompletedNeuropathy | AIDSSouth Africa
-
Vantia LtdVeeda Clinical ResearchCompleted
-
University of California, Los AngelesCompletedAutism Spectrum DisorderUnited States
-
University of California, Los AngelesCompleted
-
Jiangsu Kanion Pharmaceutical Co., LtdBeijing Bionovo Medicine Development Co., Ltd.Completed