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| ID | Type | Description | Link |
|---|---|---|---|
| CTRU protocol 1314 | |||
| IRB protocol 19373 |
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The purpose of this study is to determine the benefit of using the FDA-approved insulin-sensitizing agent, Pioglitazone, on human heart transplant recipients. The objectives of this project are to (1) determine if pioglitazone effectively treats insulin resistance in heart transplant recipients, and (2) to determine whether pioglitazone therapy after heart transplantation impacts the development or progression of cardiac allograft vasculopathy (CAV), a form of chronic rejection after heart transplantation.
CAV, a rapidly progressive obliterative disease involving the graft coronary arteries, is the leading cause of morbidity and mortality beyond the first year after heart transplantation. This common complication occurs in almost half of recipients within 3 years after heart transplantation, and is associated with high rates of graft failure and mortality. Clinical care of heart transplant recipients in the current era is greatly limited by the lack of effective treatment options to prevent or retard the progression of CAV. CAV appears to be strongly associated with the state of insulin resistance, which is present in over half of heart transplant recipients and is characterized by metabolic abnormalities including glucose intolerance, dyslipidemia, endothelial dysfunction, and high levels of circulating inflammatory markers. Insulin resistance can be effectively treated with pioglitazone, a TZD compound which directly affects tissue insulin sensitivity. In this study, we will enroll 32 insulin-resistant heart transplant recipients and will randomize them to pioglitazone or placebo for a one-year period. We will determine the efficacy of pioglitazone for the treatment of insulin resistance and prevention of the development and progression of CAV after heart transplantation. The data generated from this study will provide important preliminary data for future, larger-scale clinical investigations.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pioglitazone | Active Comparator | Pioglitazone |
|
| Placebo | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pioglitazone | Drug | 15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Insulin Levels Area Under Curve(AUC) | Change from baseline in Insulin Levels During Oral Glucose Tolerance test at 1 year. | Baseline and 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Intimal Volume | Intimal volume is defined as external elastic membrane volume minus lumen (luminal) volume measured at the heart Catheterization and intravascular Ultrasound( IVUS) | baseline and 1 year |
| Change in Levels of Fasting Glucose at Baseline and 1 Year |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kiran Khush | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University School of Medicine | Stanford | California | 94305 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Pioglitazone | Pioglitazone Pioglitazone: 15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months |
| FG001 | Placebo | Placebo Placebo: placebo taken daily for one year |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Double-blind randomized clinical trial of pioglitazone versus placebo from 2010 to 2013 in heart transplant recipients who were 1-4 years post-transplant.Eighteen heart transplant patients aged 22 to 72 years were randomized (9 to pioglitazone, 9 to placebo)
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| ID | Title | Description |
|---|---|---|
| BG000 | Pioglitazone | Pioglitazone Pioglitazone: 15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| 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 | Insulin Levels Area Under Curve(AUC) | Change from baseline in Insulin Levels During Oral Glucose Tolerance test at 1 year. | Posted | Mean | 95% Confidence Interval | h*pmol/L | Baseline and 1 year |
|
Adverse event reporting was started at first dose and approximatly one year later ( at final dose and testing) plus 30 days.
Assessment of adverse events was made by routine Comprehensive physical exam by MD, routine echocardiography, routine Comprehensive laboratory Chemistry metabolic panel, Complete Blood count, Lipid profile and all relevant drug level in the Transplant arena. In addition post GTT, research team called participant to follow up for any complaints.
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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 | Pioglitazone Pioglitazone: 15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kiran K. Khush, MD | Stanford University | 650-721-3241 | kiran@stanford.edu |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| 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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|
| Placebo | Drug | placebo taken daily for one year |
|
Oral Glucose Tolerance Test : blood was drawn for fasting plasma glucose and insulin levels, followed by ingestion of a solution containing 75grams of glucose. Repeat blood samples were collected for glucose and insulin levels at 30, 90, and 120 minutes after glucose ingestion. All glucose measurements were performed by the Clinical Translational Research Unit (CTRU) Stanford University. |
| Baseline and 1 year |
| Change From Baseline in TG/HDL Ratio at One Year | Triglyceride ratio to High Density Lipoprotien | Baseline and 1 year |
| Change in Maximal Intimal Thickness(MIT) by Intravascular Unltrasound(IVUS) | The change in maximal intimal thickness (MIT) from baseline to one year was recorded for several matched sites in the same coronary artery, the cross sections, predominantly in the left anterior descending coronary artery, from baseline to one-year follow-up, were studied. The IVUS cross sections were matched by using identifiable landmarks in the images, such as bifurcations or arterial calcification, or external landmarks, such as coronary veins or pericardium. In addition, the one-year IVUS studies were obtained with an angiographic roadmap of where the initial IVUS study was performed along the length of the vessel. The IVUS system auto pullback was performed at .5 mm/s from the mid-distal portion of the study vessel, where an easily identifiable landmark was visible (i.e., branchpoint). The following items were measured for each patient: maximal intimal thickness (MIT), intimal area (IA), and vessel area. | Baseline and 1 year |
| Change From Baseline in ADMA (Asymmetric Dimethylarginine) at One Year. | Competitive ELISA assay in Stanford laboratory. | Baseline and 1 year |
| Change From Baseline in High-sensitivity C-reactive Protein (HsCRP) at One Year | measure of low levels of C-reactive protein to identify low but persistent levels of inflammation | Baseline and 1 year |
Placebo
Placebo: placebo taken daily for one year
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Secondary | Change in Intimal Volume | Intimal volume is defined as external elastic membrane volume minus lumen (luminal) volume measured at the heart Catheterization and intravascular Ultrasound( IVUS) | The number of participants enrolled were not all included in the intimal volume analysis because the Angiographic diagnostic evaluation needed for intimal volume measurement was clinically inappropriate for 3 in the pioglitazone arm and 5 in the Placebo arm at 12 months post transplant. | Posted | Mean | Standard Deviation | mm^3 | baseline and 1 year |
|
|
|
| Secondary | Change in Levels of Fasting Glucose at Baseline and 1 Year | Oral Glucose Tolerance Test : blood was drawn for fasting plasma glucose and insulin levels, followed by ingestion of a solution containing 75grams of glucose. Repeat blood samples were collected for glucose and insulin levels at 30, 90, and 120 minutes after glucose ingestion. All glucose measurements were performed by the Clinical Translational Research Unit (CTRU) Stanford University. | One participant in each group did not complete the OGTT. | Posted | Mean | Standard Deviation | mg/dL | Baseline and 1 year |
|
|
|
| Secondary | Change From Baseline in TG/HDL Ratio at One Year | Triglyceride ratio to High Density Lipoprotien | One drop out | Posted | Mean | Standard Deviation | ratio | Baseline and 1 year |
|
|
|
| Secondary | Change in Maximal Intimal Thickness(MIT) by Intravascular Unltrasound(IVUS) | The change in maximal intimal thickness (MIT) from baseline to one year was recorded for several matched sites in the same coronary artery, the cross sections, predominantly in the left anterior descending coronary artery, from baseline to one-year follow-up, were studied. The IVUS cross sections were matched by using identifiable landmarks in the images, such as bifurcations or arterial calcification, or external landmarks, such as coronary veins or pericardium. In addition, the one-year IVUS studies were obtained with an angiographic roadmap of where the initial IVUS study was performed along the length of the vessel. The IVUS system auto pullback was performed at .5 mm/s from the mid-distal portion of the study vessel, where an easily identifiable landmark was visible (i.e., branchpoint). The following items were measured for each patient: maximal intimal thickness (MIT), intimal area (IA), and vessel area. | number participants analyzed contained drops out due to clinical reasons | Posted | Mean | Standard Deviation | mm | Baseline and 1 year |
|
|
|
| Secondary | Change From Baseline in ADMA (Asymmetric Dimethylarginine) at One Year. | Competitive ELISA assay in Stanford laboratory. | One participant in one arm did not have Baseline or one year data. | Posted | Mean | Standard Deviation | umol/L | Baseline and 1 year |
|
|
|
| Secondary | Change From Baseline in High-sensitivity C-reactive Protein (HsCRP) at One Year | measure of low levels of C-reactive protein to identify low but persistent levels of inflammation | participant drop put | Posted | Mean | Standard Deviation | mg/L | Baseline and 1 year |
|
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| EG001 | Placebo | Placebo Placebo: placebo taken daily for one year | 0 | 9 | 0 | 9 |
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| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |