Insulin Resistance in Patients With Mood Disorder

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00242619
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 29
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Insulin resistance is known to be associated with mood disorders and cognitive difficulties. The purpose of this study is to treat depressed patients with rosiglitazone (also known as [AKA] Avandia), therefore improving glucose sensitivity, which in turn has the potential to affect mood and thinking. We, the researchers at Stanford University, are recruiting men and women who have been diagnosed with depression, and are willing to participate in this 3 month study. Participation involves neuropsychological testing, 2 blood draws called an oral glucose tolerance test (OGTT), which tests for glucose and insulin levels, and the medication, rosiglitazone. Participants are allowed to continue on their current psychiatric medication.

Condition or Disease	Intervention/Treatment	Phase
Depression; Bipolar Disorder; Insulin Resistance	Drug: rosiglitazone	N/A

Detailed Description

An association between insulin resistance (IR) and affective disorders has been postulated in a number of cross-sectional studies. Limited data exist on potential changes in IR associated with improvement in depressive symptoms and/or depression remission resolution - two studies reported decreased IR after successful antidepressant treatment, while another study reported persisting IR even after successful treatment.

We have postulated that IR is a part of the pathophysiology of affective disorders, and its improvement (via pharmacological or nonpharmacological treatments) may significantly reduce the severity of depressive symptoms. In support of this hypothesis, we previously reported increased IR in women with bipolar disorder, as well as a significant association between IR and depressive symptoms in women with primary IR syndrome (polycystic ovary syndrome [PCOS]). In the current pilot study, we attempted a more direct testing of the hypothesis that improvement of IR will result in improvement in mood in patients with depressive disorders. The aim of the study was to evaluate whether addition of the peroxisome proliferator-activated receptor-γ (PPAR) agonist rosiglitazone to the treatment as usual (TAU) of nondiabetic patients with unipolar or bipolar depression would result in improvement in depression severity and clinical global impression (CGI). Insulin sensitizing agents have proven efficacious in nondiabetic IR, or "prediabetic", individuals. All subjects in this pilot study had elevated fasting plasma glucose (FPG) and ratios of high density lipoproteins (HDL) to triglycerides (TG), which are established surrogate markers of IR.

In the current pilot study, we attempted a more direct testing of the hypothesis that improvement of IR will result in improvement in mood in patients with depressive disorders. The aim of the study was to evaluate whether addition of the peroxisome proliferator-activated receptor-γ (PPAR) agonist rosiglitazone to the treatment as usual (TAU) of nondiabetic patients with unipolar or bipolar depression would result in improvement in depression severity and clinical global impression (CGI). Insulin sensitizing agents have proven efficacious in nondiabetic IR, or "prediabetic", individuals. All subjects in this pilot study had elevated fasting plasma glucose (FPG) and ratios of high density lipoproteins (HDL) to triglycerides (TG), which are established surrogate markers of IR.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Rosiglitazone Add-On in Treatment of Depressed Patients With Insulin Resistance: a Pilot Study
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rosiglitzone This group includes all 12 subjects who received rosiglitazone. Rosiglitazone was administered in addition to current antidepressant and/or mood-stabilizing medication at a dose of 4 mg/day for the first 4 weeks, with subsequent increase in dose to 9 mg/day for the remaining 8 weeks of the 12-week trial.	Drug: rosiglitazone; Rosiglitazone was administered at two different doses over the 12-week period.; Other Names: Avandia

Outcome Measures

Primary Outcome Measures

1. Hamilton Depression Rating Scale (HDRS-21) [12 weeks]

   The Hamilton Depression Rating Scale (HDRS-21) measures depression severity on a scale from 0 to 21, with 0 being the lowest level of depression severity and 21 being the highest level of depression severity.

2. Clinical Global Impression-Severity Scale (CGI-S) [12 weeks]

   The Clinical Global Impression-Severity Scale (CGI-S) assesses depression severity. It is a 7-point scale, where 1 is the lowest level of depression severity and 7 is the highest level of depression severity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:- Current depression

• Insulin resistance

• Current physician/psychiatrist care

• Between the ages of 18-60

• Willing to sign the Human Subjects Protection Consent Form

• Willing to have blood sampling Exclusion Criteria:- Diabetes

• History of unstable heat disease

• Uncontrolled hypertension

• Extensive use of alcohol

• Current use of street drugs

• History of myocardial infarction

• History of cerebrovascular disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Dr Natalie Rasgon, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Natalie Rasgon, Principal Investigator, Stanford University
• ClinicalTrials.gov Identifier: NCT00242619
• Other Study ID Numbers: 95552
• First Posted: Oct 20, 2005
• Last Update Posted: Feb 14, 2017
• Last Verified: Dec 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Insulin Resistance; Bipolar Disorder; Rosiglitazone

Study Results

Participant Flow

Arm/Group Title	Completers	Drop-Outs
Arm/Group Description	Subjects who completed the study and 12 weeks of taking rosiglitazone.	Subjects who dropped out and did not complete the 12 weeks on rosiglitazone.
Period Title: Overall Study
STARTED	8	4
COMPLETED	8	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Completers	Drop-Outs	Total
Arm/Group Description	Subjects who met all criteria, took rosiglitazone, and completed the study.	Subjects who met all criteria, took rosiglitazone, and did not complete the study.	Total of all reporting groups
Overall Participants	8	4	12
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	4 100%	12 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.9 (5.6)	52.0 (6.5)	51.95 (6.05)
Gender (Count of Participants)
Female	7 87.5%	4 100%	11 91.7%
Male	1 12.5%	0 0%	1 8.3%
Region of Enrollment (participants) [Number]
United States	8 100%	4 100%	12 100%

Outcome Measures

1. Primary Outcome

Title	Hamilton Depression Rating Scale (HDRS-21)
Description	The Hamilton Depression Rating Scale (HDRS-21) measures depression severity on a scale from 0 to 21, with 0 being the lowest level of depression severity and 21 being the highest level of depression severity.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Completers	Drop-Outs
Arm/Group Description	Subjects who completed the study.	Subjects who dropped out of the study.
Measure Participants	8	4
Mean (Standard Deviation) [units on a scale]	19.9 (5.0)	13.0 (0.8)

2. Primary Outcome

Title	Clinical Global Impression-Severity Scale (CGI-S)
Description	The Clinical Global Impression-Severity Scale (CGI-S) assesses depression severity. It is a 7-point scale, where 1 is the lowest level of depression severity and 7 is the highest level of depression severity.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Completers	Drop-Outs
Arm/Group Description	Subjects who completed the study and 12 weeks of taking rosiglitazone.	Subjects who dropped out and did not complete the 12 weeks on rosiglitazone.
Measure Participants	8	4
Mean (Standard Deviation) [units on a scale]	4.1 (0.6)	3.3 (0.5)

Adverse Events

Time Frame	Adverse event data were collected over 12 weeks.
Arm/Group Title	Completers		Drop-Outs
Arm/Group Description	Subjects who met all criteria, took rosiglitazone, and completed the study.		Subjects who met all criteria, took rosiglitazone, and did not complete the study.
All Cause Mortality
	Completers		Drop-Outs
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Completers		Drop-Outs
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Completers		Drop-Outs
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.