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

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ClinicalTrials.gov Identifier: NCT00936663
Recruitment Status : Terminated (lack of funding)
First Posted : July 10, 2009
Last Update Posted : January 17, 2018
Sponsor:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes End Stage Renal Disease Drug: Placebo Drug: Sitagliptin Phase 4

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. 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 Data Safety Monitoring Board (DSMB). Consent will be obtained prior to transplantation.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : July 2009
Primary Completion Date : May 2010
Study Completion Date : June 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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.
Placebo Comparator: placebo
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.


Outcome Measures

Primary Outcome Measures :
  1. Fasting blood glucose [ Time Frame: 1 year ]
    Change in fasting blood glucose levels, compared to baseline


Secondary Outcome Measures :
  1. HbA1c [ Time Frame: 1 year ]
    Change in HbA1c, compared to baseline

  2. estimated glomerular filtration rate (eGFR) [ Time Frame: 1 year ]
    Change in eGFR, compared to baseline

  3. Tacrolimus and Sirolimus levels [ Time Frame: 1 year ]
    Change in Tacrolimus and Sirolimus levels, compared to baseline

  4. Hypoglycemia [ Time Frame: 1 year ]
    Number of episodes of hypoglycemia (blood glucose less than 70 mg/dl)


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00936663


Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Vijay Shivaswamy, MD University of Nebraska
More Information

Publications:
Responsible Party: Vijay Shivaswamy, MD, Associate Professor, University of Nebraska
ClinicalTrials.gov Identifier: NCT00936663     History of Changes
Other Study ID Numbers: 254-09FB
First Posted: July 10, 2009    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: January 2018

Keywords provided by Vijay Shivaswamy, MD, University of Nebraska:
Diabetes
Kidney Transplant
Sitagliptin

Additional relevant MeSH terms:
Diabetes Mellitus
Kidney Failure, Chronic
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Sitagliptin Phosphate
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action