Clinical trial NCT00936663: Using Sitagliptin as a Treatment to Prevent New Onset Diabetes After Kidney Transplantation
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Type 2 Diabetes
End Stage Renal Disease
Keywords: Diabetes
Kidney Transplant
Sitagliptin
Lead sponsor: University of Nebraska
Sponsor class: OTHER
First posted: 2009-07-10
Enrollment: 3
Sex: ALL
Minimum age (years): 19
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Fasting Blood Glucose
timeFrame: 1 year
Secondary outcomes:
measure: HbA1c
timeFrame: 1 year
measure: eGFR
timeFrame: 1 year
measure: Hypoglycemia
timeFrame: 1 year
Other outcomes:
measure: AUC for Glucose
timeFrame: 1 year
measure: AUC for Insulin
timeFrame: 1 year
measure: AUC for Proinsulin
timeFrame: 1 year
measure: AUC for C Peptide
timeFrame: 1 year
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Vijay Shivaswamy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.