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

This study is enrolling participants by invitation only.
Sponsor:
Information provided by:
University of Nebraska
ClinicalTrials.gov Identifier:
NCT00936663
First received: June 25, 2009
Last updated: July 20, 2009
Last verified: July 2009
  Purpose

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.


Condition Intervention Phase
Diabetes
Kidney Transplant
Drug: Sitagliptin
Drug: Placebo
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 40
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)
Arms Assigned Interventions
Experimental: 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.
Other Name: Januvia
Placebo Comparator: Placebo Drug: Placebo
Drug will be available as 100, 50, and 25 mg size with identical placebo.
Other Name: Placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   19 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00936663

Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: James T. Lane, MD University of Nebraska
  More Information

No publications provided

Responsible Party: James T. Lane MD, University of Nebraska Medical Center
ClinicalTrials.gov Identifier: NCT00936663     History of Changes
Other Study ID Numbers: 254-09FB
Study First Received: June 25, 2009
Last Updated: July 20, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by University of Nebraska:
Diabetes
Kidney Transplant
Sitagliptin

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 26, 2014