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

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.

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.

Study Overview

• Status: Completed
• Conditions: Pre Diabetes
• Intervention / Treatment: Drug: Exenatide SR

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Exenatide SR Intervention Group; Subjects will receive, in addition to standard care, Exenatide SR 2 mg subcutaneous (SQ) weekly for 24 months.	Drug: Exenatide SR; Exenatide SR 2 mg subcutaneous (SQ) weekly
NO_INTERVENTION: Standard of Care; Subjects will receive standard post-transplant care as per Mayo Clinic usual practice.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Mark D Stegall, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 9, 2019
• Primary Completion (ACTUAL): October 18, 2021
• Study Completion (ACTUAL): October 18, 2021

Study Registration Dates

• First Submitted: April 23, 2019
• First Submitted That Met QC Criteria: May 22, 2019
• First Posted (ACTUAL): May 23, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 3, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Kidney Transplant
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Prediabetic State; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: 19-000649

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No