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Pioglitazone in Patients With Mood Disorders

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01559857
First Posted: March 21, 2012
Last Update Posted: May 10, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Institutes of Health (NIH)
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Natalie Rasgon, Stanford University
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder Insulin Resistance Drug: Pioglitazone Drug: Sugar Pill Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pioglitazone Treatment for Insulin Resistant Patients With Mood Disorders

Resource links provided by NLM:


Further study details as provided by Natalie Rasgon, Stanford University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • Fasting Insulin Measurements at Baseline [ Time Frame: Baseline ]
    The fasting plasma insulin measurements taken at baseline are shown in the data table below.

  • 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.


Enrollment: 37
Study Start Date: November 2011
Study Completion Date: June 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Pioglitazone
50% of participants will be allocated to 12 weeks of treatment with 30 mg/day of Pioglitazone.
Drug: Pioglitazone
30mg once daily for 12 weeks
Other Name: Actos
Placebo Comparator: Sugar pill
50% of participants will be randomized to 12 weeks of treatment with placebo pill.
Drug: Sugar Pill
Placebo
Other Name: Placebo

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01559857


Locations
United States, California
Stanford University Department of Psychiatry & Behavioral Sciences
Palo Alto, California, United States, 94305
Sponsors and Collaborators
Stanford University
National Institutes of Health (NIH)
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Natalie Rasgon, MD, PhD Stanford University
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Natalie Rasgon, Professor, Stanford University
ClinicalTrials.gov Identifier: NCT01559857     History of Changes
Other Study ID Numbers: R21MH093948-01A1 ( U.S. NIH Grant/Contract )
First Submitted: March 16, 2012
First Posted: March 21, 2012
Results First Submitted: October 19, 2016
Results First Posted: May 10, 2017
Last Update Posted: May 10, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Natalie Rasgon, Stanford University:
Depression
Insulin resistance
Mood disorder

Additional relevant MeSH terms:
Disease
Depressive Disorder
Depression
Depressive Disorder, Major
Insulin Resistance
Mood Disorders
Pathologic Processes
Mental Disorders
Behavioral Symptoms
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs