Efficacy Study of Sitagliptin to Prevent New-onset Diabetes After Kidney Transplant

Study Overview
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Brief Summary
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The purpose of this study is to determine whether sitagliptin is effective in preventing the development of new-onset diabetes after kidney transplant (NODAT). Up to one-third of previously non-diabetic patients develop NODAT after a kidney transplant. Corticosteroids and calcineurin inhibitors are two commonly utilized anti-rejection medications that contribute to diabetes development through multiple mechanisms; including decreased insulin production by the pancreas. Sitagliptin is an oral medication that results in increased insulin secretion. We hypothesize that administration of sitagliptin to transplant recipients identified to be at risk for diabetes development will reduce the incidence and severity of NODAT.

Detailed Description
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This will be a single-center, randomized, double-blind trial to evaluate the efficacy of sitagliptin to prevent the development of new-onset diabetes after transplant (NODAT) in previously non-diabetic patients with post-operative hyperglycemia following living-donor or deceased-donor kidney transplant. In this trial, previously non-diabetic adult patients with hyperglycemia (random blood sugar >200mg/dL) in the first 72 hours following kidney transplant will be screened to determine eligibility based on inclusion/exclusion criteria. Patients that meet study entry criteria will be stratified based on HbA1c (<5.7 or 5.7-6.4%) and randomized in a 1:1 ratio to one of two treatment groups: sitagliptin versus placebo. Fifty patients (25 per group) will be enrolled. Dosing period will be 3 months at which time study drug will be discontinued and patients will be followed for an additional 3 month period. Study visits will occur at 0, 1, 3 and 6 months. A HbA1c and 2-hour oral glucose tolerance test (OGTT) will be obtained at the 3 and 6 month study visit. Screening period (Visit 1) All patients presenting for living-donor or deceased donor kidney transplant will have a medical history, medication history, vital signs, height, weight, body mass index, physical exam, random blood sugar (BS), HbA1c and EKG done as part of routine pre-transplant protocol at Barnes Jewish Hospital. Patients with hyperglycemia, defined as a random blood sugar ≥ 200 mg/dL, in the first 72 hours after kidney transplant will be screened to determine eligibility for the study based on inclusion and exclusion criteria. Randomization (Visit 2) Patients meeting study entry criteria and consenting to study participation will be stratified based on HbA1c (<5.7 or 5.7-6.4%) and block randomized in blocks of eight in a 1:1 ratio to sitagliptin versus placebo. Sitagliptin dose will be 100mg/day, adjusted per creatinine clearance and tolerability. Patients will be instructed by a licensed diabetic educator on proper measurement and recording of fasting and post-prandial blood sugars. Subjects will be provided a log, standard glucometer and testing strips to maintain a blood sugar log post-discharge. Visit 2 will occur within 24 hours after Visit 1. Drug dosing period (Visits 3-4) Sitagliptin or placebo will be continued until 3 months post-transplant, at which time study medication will be discontinued and collected from the subject. At the 1 and 3 month visits, vital signs, height, weight, and BMI will be obtained. A physical exam will be performed. Blood sugar logs provided by the patient will be reviewed and adverse effects recorded. At the 3 month visit (Visit 4), a HbA1c, 2-hour OGTT, fasting C-peptide and insulin level will be obtained. Follow-up (Visit 5) At the 6 month final visit, 3 months following discontinuation of study medication, vital signs, height, weight, BMI, HbA1c, 2-hour OGTT, fasting C-peptide and insulin level will be obtained. A physical exam will be performed. Blood sugar logs provided by the patient will be reviewed and adverse effects recorded.

Official Title
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A Single Center, Randomized, Double-blind Controlled Trial of Sitagliptin Versus Placebo to Reduce the Incidence and Severity of New-onset Diabetes After Kidney Transplant

Conditions
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Posttransplant Diabetes Mellitus

Intervention / Treatment
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* Drug: Sitagliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (≥18 yo) recipient of living-donor or deceased donor kidney transplant Blood sugar ≥ 200 mg/dL in first 72 hours after transplant No history of diabetes or prior treatment with insulin or oral hypoglycemic agents Exclusion Criteria: A1c of ≥6.5% measured immediately pre-transplant Recipient of simultaneous kidney-pancreas, kidney-liver, kidney-heart, or kidney-lung transplant Prior non-renal solid organ transplant

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sitagliptin<br>Sitaglipitin tablets will be administered orally for 3 months from randomization Initial dose will be 100mg/daily, adjusted per renal function: Creatinine clearance > or = 50mL/min: 100mg/day Creatinine clearance > or = 30 and <50mL/min: 50mg/day Creatinine clearance <30 mL/min or on dialysis: 25mg/day | Drug: Sitagliptin<br> <br> * Other names: Januvia;|
| Placebo Comparator: Placebo<br>Placebo tablets (identical to active comparator in appearance) will be administered orally for 3 months. Starting dose and adjustment based on renal function will be identical to active comparator | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-hour Oral Glucose Tolerance Test-derived Blood Sugar | Change in 2-hour OGTT-derived blood sugar will be measured at three months and again at six months. These are 3 month OGTT results | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normal 2-hour Oral Glucose Tolerance Test-derived Blood Sugar | Number of subjects who have normal 2-hour oral glucose tolerance test-derived blood sugar will be measured at 3 months | 3 months | 
| 6 Month OGTT Result (Completion of Washout From Study Drug) | We tested another OGTT at 6 months into study, after a 3 month washout from the study drug. Study drug was discontinued after the 3 month OGTT was completed. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, transplant, kidney