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| ID | Type | Description | Link |
|---|---|---|---|
| R01DK074828 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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The purpose of this study is to determine predictors of response to pioglitazone, an anti-diabetic medication. The investigators know from randomized clinical trials that some 30% of patients do not respond to this type of medication. There is presently no way to identify this group of patients leading to unnecessary drug exposure and medication costs.
In phase I, subjects who are eligible based on height and weight and general health information will sign informed consent. In phase II, subjects will be screened to ensure that they fit the inclusion/exclusion criteria, including an oral glucose tolerance test. Other blood tests will be performed to check complete blood count, lipids, liver functions and electrolytes.
Qualifying volunteers will enter phase III, which will consist of outpatient radioimaging and body composition, metabolic testing (intravenous glucose tolerance test), and tissue biopsies. Blood will also be drawn for genetic testing and for microarray studies of leukocytes. Written medication information and instructions for pioglitazone, discharge instructions and satisfaction surveys following the tissue biopsy procedures will be given to subjects during the study. During phase IV, subjects will begin pioglitazone therapy. Every 4 weeks throughout the drug intervention, glycemic control, lipoprotein profile, and weight will be monitored. After 12 weeks of pioglitazone therapy, the X-ray and magnetic resonance (MR) measurements of body composition, the biopsies and the metabolic tests performed during phase III will be repeated (phase V), and blood will be drawn for microarray studies of leukocytes.
Thereafter, subjects will have the option to be enrolled in a 10 week, behavioral weight loss program (phase VI). Following the 10-week weight loss program, a few outcome measurements will be repeated (phase VII).
Throughout the study, Women of Child Bearing Potential (WCBP) will have human human chorionic gonadotrophin (HCG) urine pregnancy tests. Pregnancy tests will only be performed on Women of childbearing potential, meaning women who are pre-menopausal and who have not had surgical sterilization. Women who have not had a hysterectomy or tubal ligation at least six months prior to signing informed consent or have been postmenopausal for at least one year, will be instructed to practice one of the following methods of birth control throughout the study: oral, transdermal, or implantable hormonal contraceptives, intrauterine device, diaphragm plus spermicide, condom plus spermicide, or abstinence. Pioglitazone may reduce the effectiveness of some hormonal types of contraceptives. Women using hormonal methods of birth control will be advised to use a barrier method as well. Female subjects are informed to notify the investigators immediately if they think they might have become pregnant during the study.
Participants who are eligible have 10 visits over an approximate 15-week period. Participants can choose to participate in an optional weight management program for an additional 10 weeks after treatment and before their final visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pioglitazone (Actos) | Experimental | Participants will have metabolism studies to consist of outpatient X-ray and MR measurements of bone density and body composition, metabolic testing (intravenous glucose tolerance test), and muscle and adipose tissue biopsies. Blood will also be drawn for genetic testing and for microarray studies of leukocytes. Upon completion of the above studies, the participant will begin pioglitazone therapy. Every 4 weeks throughout the drug intervention, glycemic control, lipoprotein profile, and weight will be monitored. After 12 weeks of pioglitazone therapy, the X-ray and MR measurements of body composition, the biopsies, microarray studies for leukocytes and the metabolic tests will be repeated. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pioglitazone | Drug | 30 mg tablet once daily for 4 weeks, then increased to 45 mg once daily for an additional 8 weeks. Total dosage period is 12 weeks. |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in Insulin Resistance | Change in insulin resistance was calculated as change (end of treatment minus baseline) in HOMA-IR index (glucose (mg/dL) x insulin (μU/mL)/405) | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Genes Determined to be Correlated With Change in Insulin Sensitivity | Number of genes determined to be correlated with change in insulin sensitivity as determined by HOMA-IR with a p-value below 0.000001 | 12 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Soren Snitker, MD, PhD | University of Maryland, Baltimore | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Maryland School of Medicine | Baltimore | Maryland | 21201 | United States |
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Screening assessments done following informed consent include anthropometry, screening bloodwork, medical history and baseline study assessments. Participants may be excluded prior to start of study drug and/or baseline assessments if they do not meet eligibility criteria.
Recruitment was through advertisements in local publications and bulletin boards in the University of Maryland and Baltimore area. Additional recruitment among the Old Order Amish was through the University of Maryland Amish Research Clinic in Lancaster County, Pennsylvania.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pioglitazone (Actos) | Participants will have metabolism studies to consist of outpatient X-ray and magnetic resonance (MR) measurements of bone density and body composition, metabolic testing (intravenous glucose tolerance test), and muscle and adipose tissue biopsies. Blood will also be drawn for genetic testing and for microarray studies of leukocytes. Upon completion of the above studies, the participant will begin pioglitazone therapy. Every 4 weeks throughout the drug intervention, glycemic control, lipoprotein profile, and weight will be monitored. After 12 weeks of pioglitazone therapy, the X-ray and MR measurements of body composition, the biopsies, microarray studies for leukocytes and the metabolic tests will be repeated. Pioglitazone: 30 mg tablet once daily for 4 weeks, then increased to 45 mg once daily for an additional 8 weeks. Total dosage period is 12 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Screening |
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| Baseline Assessment |
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| Study Treatment |
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| ID | Title | Description |
|---|---|---|
| BG000 | Pioglitazone (Actos) | Participants will have metabolism studies to consist of outpatient X-ray and MR measurements of bone density and body composition, metabolic testing (intravenous glucose tolerance test), and muscle and adipose tissue biopsies. Blood will also be drawn for genetic testing and for microarray studies of leukocytes. Upon completion of the above studies, the participant will begin pioglitazone therapy. Every 4 weeks throughout the drug intervention, glycemic control, lipoprotein profile, and weight will be monitored. After 12 weeks of pioglitazone therapy, the X-ray and MR measurements of body composition, the biopsies, microarray studies for leukocytes and the metabolic tests will be repeated. Pioglitazone: 30 mg tablet once daily for 4 weeks, then increased to 45 mg once daily for an additional 8 weeks. Total dosage period is 12 weeks. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Insulin Resistance | Change in insulin resistance was calculated as change (end of treatment minus baseline) in HOMA-IR index (glucose (mg/dL) x insulin (μU/mL)/405) | Included subjects are those who had complete data, including HOMA-IR index at both baseline and after treatment. | Posted | Mean | Standard Deviation | HOMA-IR index is unitless by definition | 12 weeks |
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|
12 weeks (treatment phase) + 4 weeks (follow-up) = 16 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pioglitazone (Actos) | Participants will have metabolism studies to consist of outpatient X-ray and MR measurements of bone density and body composition, metabolic testing (intravenous glucose tolerance test), and muscle and adipose tissue biopsies. Blood will also be drawn for genetic testing and for microarray studies of leukocytes. Upon completion of the above studies, the participant will begin pioglitazone therapy. Every 4 weeks throughout the drug intervention, glycemic control, lipoprotein profile, and weight will be monitored. After 12 weeks of pioglitazone therapy, the X-ray and MR measurements of body composition, the biopsies, microarray studies for leukocytes and the metabolic tests will be repeated. Pioglitazone: 30 mg tablet once daily for 4 weeks, then increased to 45 mg once daily for an additional 8 weeks. Total dosage period is 12 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hypoglycemia | Endocrine disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hematoma at abdominal fat biopsy site | Skin and subcutaneous tissue disorders | Systematic Assessment | Hematoma at abdominal fat biopsy site |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Soren Snitker, MD, PhD | University of Maryland School of Medicine | 4107061511 | ssnitker@som.umaryland.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 27, 2006 | Apr 27, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000077205 | Pioglitazone |
| ID | Term |
|---|---|
| D045162 | Thiazolidinediones |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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| Physician Decision |
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| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Insulin resistance | Homeostatic Model of Insulin Resistance (HOMA-IR) index was calculated as (glucose (mg/dL) x insulin (μU/mL)/405) based on an intravenous glucose tolerance test as per Turner et al.* By definition, HOMA-IR index is unitless. *Turner R.C., et al. (1979). "Insulin deficiency and insulin resistance interaction in diabetes: estimation of their relative contribution by feedback analysis from basal plasma insulin and glucose concentrations". Metabolism. 28 (11): 1086-96 | HOMA-IR index was calculated only on subjects who had complete data including both intravenous glucose tolerance tests | Mean | Standard Deviation | HOMA-IR index is unitless by definition |
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| Counts |
|---|
| Participants |
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| Secondary | Number of Genes Determined to be Correlated With Change in Insulin Sensitivity | Number of genes determined to be correlated with change in insulin sensitivity as determined by HOMA-IR with a p-value below 0.000001 | Only subjects who had complete RNAseq (RNA sequencing) data and HOMA-IR were included | Posted | Number | Genes | 12 weeks | Genes | Genes |
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|
| 0 |
| 114 |
| 2 |
| 114 |
| 15 |
| 114 |
| Vasovagal response | Cardiac disorders | Non-systematic Assessment | bradycardia secondary to vasovagal response during fat biopsy |
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| Hypoglycemia during intravenous glucose tolerance test | Endocrine disorders | Systematic Assessment | Hypoglycemia during intravenous glucose tolerance test |
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| D004700 | Endocrine System Diseases |
| D006946 | Hyperinsulinism |
| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |