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lack of funding
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This study is designed to see if the use of the drug Sitagliptin (used to reduce insulin resistance) will delay or prevent kidney transplant patients from getting diabetes.
New-onset diabetes after transplantation (NODAT) is a complication of solid organ transplantation. In the University of Nebraska Medical Center (UNMC) Kidney-Pancreas Transplant Clinic, the frequency of this complication exceeds 50% of kidney transplant recipients without diabetes prior to transplantation. NODAT is associated with increased morbidity and mortality. As this complication appears to occur rather soon after transplantation, potential preventative strategies need to be instituted soon after transplantation. Although traditional risk factors, such as family history, obesity, and minority status, explain some of the additional risk, it is thought that the immunosuppressive agents themselves are responsible for the increased risk of NODAT. The immunosuppressive agents are needed to prevent rejection, and we are left to consider additional strategies to prevent the onset of NODAT. This is a pilot study utilizing the dipeptidyl peptidase-4 inhibitor, sitagliptin, in a randomized, double-blinded, placebo-controlled study in consecutive kidney transplant recipients at the University of Nebraska Medical Center. Sitagliptin has been tested in patients with type 2 diabetes who have received a kidney transplant and have shown no major side effects or alterations in immunosuppressive drug levels. This agent is FDA-approved for the treatment of type 2 diabetes, but it has a low rate of hypoglycemia. It is thought to work by inhibiting the enzyme that naturally breaks down glucagons-like peptide-1 (GLP-1), thus increasing endogenous levels of GLP-1. GLP-1 inhibits glucagons and has stimulatory effects on beta cell function. Although the current study will treat all non-diabetic patients in the hope that NODAT is delayed or prevented, this incretin-based therapy is thought to have a low risk for hypoglycemia and other side effects. In addition, it can be safely used during low-GFR conditions. The study will attempt to recruit 40 subjects (20 sitagliptin and 20 control subjects). Patients will initiate placebo or control at 2 weeks after transplantation. Subjects will be followed in the UNMC Transplant Clinic. Initially, patients will be seen weekly and later will be followed every three months for up to 1 year. The primary outcome is the development of NODAT based on the 2003 Consensus International Guidelines. Fasting glucose levels will be followed according to usual post-transplant monitoring with testing as frequently as weekly during the recent post-transplant period and eventually going to at least monthly. Secondary outcomes include HbA1c values and glucose, insulin, C-peptide, and proinsulin levels after a 75 oral glucose load that will be obtained at baseline and then every three months. In addition, side effects, including hypoglycemia, will be followed. The study will have a local Data Safety Monitoring Board (DSMB). Consent will be obtained prior to transplantation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sitagliptin 100 mg daily | Experimental | sitagliptin 100 mg daily |
|
| placebo | Placebo Comparator | placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Active drug dose will be 100 mg per day for estimated GFR above 50 ml/min. The dose will be decreased to 50 mg per day for estimated GFR 30-50 ml/min. The dose will be decreased further to 25 mg for those with estimated GFR below 30 ml/min or on dialysis. |
| Measure | Description | Time Frame |
|---|---|---|
| Fasting Blood Glucose | Fasting blood glucose levels at 1 year | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| HbA1c | HbA1c at 1 year | 1 year |
| eGFR | estimated glomerular filtration rate (eGFR) at 1 year | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| AUC for Glucose | Area Under the Curve for glucose after OGTT | 1 year |
| AUC for Insulin | Area Under the Curve for insulin after OGTT | 1 year |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Vijay Shivaswamy, MD | University of Nebraska | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Nebraska Medical Center | Omaha | Nebraska | 68198 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22067216 | Background | Lane JT, Odegaard DE, Haire CE, Collier DS, Wrenshall LE, Stevens RB. Sitagliptin therapy in kidney transplant recipients with new-onset diabetes after transplantation. Transplantation. 2011 Nov 27;92(10):e56-7. doi: 10.1097/TP.0b013e3182347ea4. No abstract available. |
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1 subject consented, but dropped out as she was too busy to participate in the study
recruitment period: 10/2009 to 8/2012 Recruitment location: Transplant Clinic and Nebraska Medicine Hospital
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| ID | Title | Description |
|---|---|---|
| FG000 | Sitagliptin 100 mg Daily | sitagliptin 100 mg daily Sitagliptin: Active drug dose will be 100 mg per day for estimated GFR above 50 ml/min. The dose will be decreased to 50 mg per day for estimated GFR 30-50 ml/min. The dose will be decreased further to 25 mg for those with estimated GFR below 30 ml/min or on dialysis. |
| FG001 | Placebo | placebo Placebo: Active drug dose will be 100 mg per day for estimated GFR above 50 ml/min. The dose will be decreased to 50 mg per day for estimated GFR 30-50 ml/min. The dose will be decreased further to 25 mg for those with estimated GFR below 30 ml/min or on dialysis. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sitagliptin 100 mg Daily | sitagliptin 100 mg daily Sitagliptin: Active drug dose will be 100 mg per day for estimated GFR above 50 ml/min. The dose will be decreased to 50 mg per day for estimated GFR 30-50 ml/min. The dose will be decreased further to 25 mg for those with estimated GFR below 30 ml/min or on dialysis. |
| BG001 |
| 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 | Fasting Blood Glucose | Fasting blood glucose levels at 1 year | Posted | Mean | Standard Deviation | mg/dl | 1 year |
|
2.5 years
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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 | Sitagliptin 100 mg Daily | sitagliptin 100 mg daily Sitagliptin: Active drug dose will be 100 mg per day for estimated GFR above 50 ml/min. The dose will be decreased to 50 mg per day for estimated GFR 30-50 ml/min. The dose will be decreased further to 25 mg for those with estimated GFR below 30 ml/min or on dialysis. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Non-Fatal Myocardial Infarction | Cardiac disorders | Standard Terminology | Non-systematic Assessment | Acute anterior wall myocardial infarction on January 29, 2012. Patient has chronic kidney disease, long standing hypertension and anemia which are known risk factors for cardiovascular disease. |
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We did not reach the target number of participants needed to achieve target power and statistically reliable results as the funding was not renewed by the sponsor.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Vijay Shivaswamy | University of Nebraska Medical Center | 402-559-6208 | vshivaswamy@unmc.edu |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D007676 | Kidney Failure, Chronic |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D000068900 | Sitagliptin Phosphate |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Sitagliptin | Drug | Active drug dose will be 100 mg per day for estimated GFR above 50 ml/min. The dose will be decreased to 50 mg per day for estimated GFR 30-50 ml/min. The dose will be decreased further to 25 mg for those with estimated GFR below 30 ml/min or on dialysis. |
|
| Hypoglycemia | Number of episodes of hypoglycemia (blood glucose less than 70 mg/dl) | 1 year |
| AUC for Proinsulin | Area Under the Curve for Proinsulin after OGTT | 1 year |
| AUC for C Peptide | Area Under the Curve for C peptide after OGTT | 1 year |
| Placebo |
placebo Placebo: Active drug dose will be 100 mg per day for estimated GFR above 50 ml/min. The dose will be decreased to 50 mg per day for estimated GFR 30-50 ml/min. The dose will be decreased further to 25 mg for those with estimated GFR below 30 ml/min or on dialysis. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants | No |
|
| HbA1c | Mean | Standard Deviation | percentage of glycated haemoglobin |
|
| Fasting Blood Glucose | Mean | Standard Deviation | mg/dl |
|
| estimated glomerular filtration rate (eGFR) | Mean | Standard Deviation | mL/min/1.73 m² |
|
| Area Under the Curve (AUC) for glucose | Baseline OGTT was not performed in one patient in Sitagliptin group and one patient in placebo group Reason was not documented | Mean | Standard Deviation | mg*hr/dl |
|
| AUC for Insulin | Baseline OGTT was not performed in one patient in Sitagliptin group and one patient in placebo group Reason was not documented | Mean | Standard Deviation | mciu*hr/ml |
|
| AUC Proinsulin | Baseline OGTT was not performed in one patient in Sitagliptin group and one patient in placebo group Reason was not documented | Mean | Standard Deviation | pmol*hr/L |
|
| AUC C peptide | Baseline OGTT was not performed in one patient in Sitagliptin group and one patient in placebo group Reason was not documented | Mean | Standard Deviation | ng*hr/ml |
|
|
|
| Secondary | HbA1c | HbA1c at 1 year | Posted | Mean | Standard Deviation | percentage of glycated haemoglobin | 1 year |
|
|
|
| Secondary | eGFR | estimated glomerular filtration rate (eGFR) at 1 year | Posted | Mean | Standard Deviation | mL/min/1.73 m² | 1 year |
|
|
|
| Secondary | Hypoglycemia | Number of episodes of hypoglycemia (blood glucose less than 70 mg/dl) | Posted | Mean | Standard Deviation | episodes | 1 year |
|
|
|
| Other Pre-specified | AUC for Glucose | Area Under the Curve for glucose after OGTT | Posted | Mean | Standard Deviation | mg*hr/dl | 1 year |
|
|
|
| Other Pre-specified | AUC for Insulin | Area Under the Curve for insulin after OGTT | Posted | Mean | Standard Deviation | mciu*hr/ml | 1 year |
|
|
|
| Other Pre-specified | AUC for Proinsulin | Area Under the Curve for Proinsulin after OGTT | Posted | Mean | Standard Error | pmol*hr/L | 1 year |
|
|
|
| Other Pre-specified | AUC for C Peptide | Area Under the Curve for C peptide after OGTT | Posted | Mean | Standard Deviation | ng*hr/ml | 1 year |
|
|
|
| 0 |
| 1 |
| 1 |
| 1 |
| 0 |
| 1 |
| EG001 | Placebo | placebo Placebo: Active drug dose will be 100 mg per day for estimated GFR above 50 ml/min. The dose will be decreased to 50 mg per day for estimated GFR 30-50 ml/min. The dose will be decreased further to 25 mg for those with estimated GFR below 30 ml/min or on dialysis. | 0 | 2 | 0 | 2 | 0 | 2 |
|
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| D051436 | Renal Insufficiency, Chronic |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011719 |
| Pyrazines |
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|