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

• ClinicalTrials.gov Identifier: NCT00936663
• Recruitment Status: Terminated
• First Posted: July 10, 2009
• Results First Posted: April 24, 2018
• Last Update Posted: April 24, 2018
• Sponsor: University of Nebraska
• Information provided by (Responsible Party): Vijay Shivaswamy, MD, University of Nebraska

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 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, 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: 3 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
• Actual Primary Completion Date: May 2010
• Actual Study Completion Date: June 2010

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 ]
   Fasting blood glucose levels at 1 year

Secondary Outcome Measures :

1. HbA1c [ Time Frame: 1 year ]
   HbA1c at 1 year
2. eGFR [ Time Frame: 1 year ]
   estimated glomerular filtration rate (eGFR) at 1 year
3. Hypoglycemia [ Time Frame: 1 year ]
   Number of episodes of hypoglycemia (blood glucose less than 70 mg/dl)

Other Outcome Measures:

1. AUC for Glucose [ Time Frame: 1 year ]
   Area Under the Curve for glucose after OGTT
2. AUC for Insulin [ Time Frame: 1 year ]
   Area Under the Curve for insulin after OGTT
3. AUC for Proinsulin [ Time Frame: 1 year ]
   Area Under the Curve for Proinsulin after OGTT
4. AUC for C Peptide [ Time Frame: 1 year ]
   Area Under the Curve for C peptide after OGTT

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 70 Years (Adult, Older Adult)
• 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

Locations

United States, Nebraska

University of Nebraska Medical Center

Omaha, Nebraska, United States, 68198

Sponsors and Collaborators

University of Nebraska

Investigators

• Principal Investigator: Vijay Shivaswamy, MD; University of Nebraska

More Information

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.

• Responsible Party: Vijay Shivaswamy, MD, Associate Professor, University of Nebraska
• ClinicalTrials.gov Identifier: NCT00936663
• Other Study ID Numbers: 254-09FB
• First Posted: July 10, 2009
• Results First Posted: April 24, 2018
• Last Update Posted: April 24, 2018
• Last Verified: March 2018

Keywords provided by Vijay Shivaswamy, MD, University of Nebraska:

Diabetes; Kidney Transplant; Sitagliptin

Additional relevant MeSH terms:

Kidney Failure, Chronic; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; 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