Assess the Efficacy and Safety of Exenatide SR for the Prevention of Diabetes After Kidney Transplantation

Study Overview
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Brief Summary
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Researchers are trying to determine if an anti-diabetes medication, called Exenatide SR, is well tolerated in kidney transplant patients with elevated blood glucose levels, and if it's effective in preventing diabetes.

Detailed Description
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New diabetes can develop after transplant and may affect a transplanted kidney's health and a recipient's overall health. Currently, patients who are pre-diabetic are encouraged to exercise and lose weight. Researchers are planning to test whether an addition of this medication will lead to better results and more effectively prevent diabetes in patients who already have high blood sugars. Exenatide SR is medication given by weekly injection. It increases insulin release in response to a meal and slows digestion. This medicine is already in use and approved by the US Food and Drug Administration (FDA) in patients with diabetes. However, it has not been approved for this indication; the FDA has allowed the use of this drug in this research study.

Official Title
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A Phase 2, Prospective, Randomized, Multicenter, Open-Label, Controlled Trial to Assess the Efficacy and Safety of Exenatide SR for the Prevention of Diabetes After Kidney Transplantation.

Conditions
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Pre Diabetes

Intervention / Treatment
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* Drug: Exenatide SR


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Recipients of solitary kidney transplants (i.e. not combined liver-kidney, pancreas-kidney etc.) At 4 months after transplantation: Prediabetes (fasting blood glucose 100-125 mg/dl; or 2 hr glucose 140-199 or HgbA1c 5.7-6.4%) Exclusion criteria: Diabetes pre-transplantation Diabetes at 4 months <18 years of age eGFR <30 ml/min (estimated by MDRD equation from serum creatinine) Active acute cellular rejection including borderline (If treated and resolved, these patients can be included) BK nephropathy active History of pancreatitis, pre-existing moderate-to-severe gastroparesis, liver cirrhosis or family /personal history of multiple endocrine neoplasia 2 or medullary thyroid cancer Pregnant or breastfeeding women. Female Subject must be either: Of non-child bearing potential: Post-menopausal (defined as at least 1 year without any menses) prior to screening , or documented surgically sterile or status post-hysterectomy Or if childbearing potential, agree not to try and become pregnant during the study for at least 90 days after the final study drug administration. And have a negative serum or urine pregnancy test. And if heterosexually active, agree to consistently use two forms of highly effective birth control. Hypersensitivity to Exenatide

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide SR Intervention Group<br>Subjects will receive, in addition to standard care, Exenatide SR 2 mg subcutaneous (SQ) weekly for 24 months. | Drug: Exenatide SR<br>* Exenatide SR 2 mg subcutaneous (SQ) weekly<br>|
| No Intervention: Standard of Care<br>Subjects will receive standard post-transplant care as per Mayo Clinic usual practice. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression From Prediabetes to Diabetes | Number of subjects to have an increase in HbA1C or fasting blood sugar to diabetic range based on the American Diabetes Association (ADA) criteria after kidney transplantation | 12 months after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression From Prediabetes to Diabetes | Number of subjects to have an increase in HbA1C or fasting blood sugar to diabetic range based on the American Diabetes Association (ADA) criteria after kidney transplantation | 24 months after transplantation | 
| Creatinine | A creatinine blood test measures the level of creatinine in the blood. Creatinine is a waste product that forms when creatine, which is found in the muscle, breaks down. Creatinine levels in the blood can provide the doctors with information about how well the kidneys are working. As measured in mg/dL units. | From enrollment, up to 20 months post-enrollment | 
| Hemoglobin A1c | Hemoglobin is a protein within red blood cells. As glucose enters the bloodstream, it binds to hemoglobin, or glycates. The more glucose that enters the bloodstream, the higher the amount of glycated hemoglobin. An A1C level below 5.7 percent is considered normal. | 12 and 24 months after kidney transplantation | 
| Incidence of Mesangial Expansion | Number of subjects to experience mesangial expansion >20%. Mesangial expansion occurs due to increased deposition of extracellular matrix proteins, for example fibronectin, into the mesangium. Accumulation of extracellular matrix proteins then occurs due to insufficient degradation by matrix metalloproteinases. | 12 and 24 months after kidney transplantation | 
| Incidence of Death | Number of subjects to experience death by any cause | From enrollment, up to 20 months post-enrollment | 
| Graft Loss | The number of subjects to experience graft loss. Primary graft failure is defined as no evidence of engraftment or hematological recovery of donor cells, within the first month after transplant, without evidence of disease relapse. Secondary graft failure refers to the loss of a previously functioning graft, resulting in cytopenia involving at least two blood cell lineages. | From enrollment, up to 20 months post-enrollment | 
| Adverse Events for Exenatide SR Intervention | Total number of adverse events reported by the subjects that received the Exenatide SR Intervention | 12 months | 

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