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

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

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.

Study Overview

• Status: Terminated
• Conditions: End Stage Renal Disease; Type 2 Diabetes
• Intervention / Treatment: Drug: Sitagliptin; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: 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.
Experimental: Sitagliptin 100 mg daily; sitagliptin 100 mg daily	Drug: 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	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
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

Collaborators and Investigators

• Sponsor: University of Nebraska
• Investigators: Principal Investigator: Vijay Shivaswamy, MD, University of Nebraska

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2009
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: June 25, 2009
• First Submitted That Met QC Criteria: July 9, 2009
• First Posted (Estimated): July 10, 2009

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: August 21, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Diabetes; Sitagliptin; Kidney Transplant
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Mellitus; Kidney Failure, Chronic; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: 0254-09-FB