Using Sitagliptin as a Treatment to Prevent New Onset Diabetes After Kidney Transplantation
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 Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||A Randomized, Placebo-Controlled Double-Blind Trial Using Sitagliptin as a Treatment to Prevent New Onset Diabetes After Kidney Transplantation: A Pilot Study|
- The primary objective of the study is to determine the ability of sitagliptin to prevent new-onset of diabetes after kidney transplantation. Information from this pilot study will be used to develop a larger study to test this intervention [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- The secondary objectives of the study will be to determine safety profile and tolerability of the intervention in a population of kidney transplant recipients. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- AUC-glucose, AUCC-peptide, AUC-insulin will also be obtained by performing routine oral glucose tolerance testing every 3 months to give an indication of insulin resistance and beta cell function. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2009|
|Estimated Study Completion Date:||June 2011|
|Estimated Primary Completion Date:||June 2010 (Final data collection date for primary outcome measure)|
|Experimental: Sitagliptin 100 mg daily||
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.
Other Name: Januvia
|Placebo Comparator: Placebo||
Drug will be available as 100, 50, and 25 mg size with identical placebo.
Other Name: Placebo
New-onset diabetes after transplantation (NODAT) is a complication of solid organ transplantation. In the 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. We propose to conduct 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. We have tested sitagliptin 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 that will be obtained at baseline and then every three months. In addition, we will follow side effects, including hypoglycemia. The study will have a local DSMB. Consent will be obtained prior to transplantation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00936663
|Principal Investigator:||James T. Lane, MD||University of Nebraska|