Using Sitagliptin as a Treatment to Prevent New Onset Diabetes After Kidney Transplantation

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Randomized, Placebo-Controlled Double-Blind Trial Using Sitagliptin as a Treatment to Prevent New Onset Diabetes After Kidney Transplantation: A Pilot Study

Conditions
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Type 2 Diabetes, End Stage Renal Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: Sitagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipient of a kidney transplant at UNMC, including cadaveric or living donor transplant. Exclusion Criteria: A previous diagnosis of diabetes or previous criteria for diabetes, according to the American Diabetes Association, not previously recognized as diabetes. Simultaneous transplant of another solid organ, such liver or heart. Patient unable to take oral medication. Patient unable to give informed consent. Hypersensitivity to sitagliptin.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin 100 mg daily<br>sitagliptin 100 mg daily | Drug: Sitagliptin<br>* 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.<br>|
| Placebo Comparator: placebo<br>placebo | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Blood Glucose | Fasting blood glucose levels at 1 year | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c | HbA1c at 1 year | 1 year | 
| eGFR | estimated glomerular filtration rate (eGFR) at 1 year | 1 year | 
| Hypoglycemia | Number of episodes of hypoglycemia (blood glucose less than 70 mg/dl) | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Kidney Transplant, Sitagliptin