Sitagliptin in Renal Transplant Recipients

The Effect of Sitagliptin Treatment on Glucose Metabolism and Endothelial Function in Renal Transplant Recipients - JANUVIA-08

The major cause of premature death in renal transplant recipients is cardiovascular disease. Sitagliptin stimulates insulin secretion and inhibits glucagon release, two central mechanisms in PTDM by interaction with a hormone system (incretins) that just recently it has become possible to modulate by drugs. Sitagliptin therefore is an interesting additional drug for the treatment of posttransplant diabetes mellitus in transplanted patients.

The primary objective of the present study is to investigate the effect of sitagliptin on insulin secretion in renal transplant recipients.

Secondary objectives are to study the effect on insulin sensitivity, fasting blood glucose, endothelial function, CsA/Tac blood concentrations.

Study Overview

• Status: Completed
• Conditions: Glucose Intolerance
• Intervention / Treatment: Drug: sitagliptin; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0027
    • Rikshospitalet Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Renal transplant recipient more than 1 year posttransplant with stable renal function (less than 20% deviation in serum creatinine the last 2 months) and stable prednisolone dose for the last 3 months before inclusion.

• Patients in need of (additional) oral anti-diabetic treatment:

  • New onset diabetes patients with fasting plasma glucose 7-8 mmol/ l, and/or 2-hr plasma glucose 12-18 mmol/l after an oral glucose tolerance test (OGTT)
  • Patients already on oral hypoglycemic therapy, but with HbA1c 8-11%
• 18 years of age.
• Male patient, or female patient without childbearing potential (surgically sterilized or postmenopausal) or, if female of childbearing potential, is not lactating, has a negative pregnancy test at screening and is willing to utilize an effective method of contraception throughout the study period and for 90 Days following discontinuation of the Study Drugs.
• Signed informed consent.

Exclusion Criteria:

• Treatment with insulin
• Severe liver disease.
• Estimated GFR < 25 ml/min/1.73 m2.
• Skin disorders that may influence laser Doppler flowmetry investigations.
• Pregnant or nursing mothers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Patients will receive 4 weeks of treatment with sitagliptin once daily	Drug: sitagliptin; Once daily sitagliptin. If GFR>50 ml/min/1.73m2: 100 mg/day. If GFR from 25 to 49 ml/min/1.3m2: 50 mg/day; Other Names: Januvia
Placebo Comparator: B; No treatment for 4 weeks	Drug: placebo; No active sitagliptin treatment for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Insulin secretion	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Insulin sensitivity	4 weeks
Fasting blood glucose	4 weeks
Endothelial function	4 weeks
Cyclosporine/tacrolimus blood concentrations	4 weeks

Collaborators and Investigators

• Sponsor: University of Oslo School of Pharmacy
• Collaborators: Oslo University Hospital
• Investigators: Principal Investigator: Trond Jenssen, MD, Professor, Rikshospitalet Medical Center

Publications and helpful links

General Publications

• Lo C, Toyama T, Oshima M, Jun M, Chin KL, Hawley CM, Zoungas S. Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients. Cochrane Database Syst Rev. 2020 Jul 30;8(8):CD009966. doi: 10.1002/14651858.CD009966.pub3.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: August 21, 2008
• First Submitted That Met QC Criteria: August 22, 2008
• First Posted (Estimate): August 25, 2008

Study Record Updates

• Last Update Posted (Estimate): September 25, 2012
• Last Update Submitted That Met QC Criteria: September 21, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: diabetes; glucose intolerance; renal transplantation; impaired glucose tolerance
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Glucose Intolerance; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: JANUVIA-08