Efficacy Study of Sitagliptin to Prevent New-onset Diabetes After Kidney Transplant

NCT01928199 | Completed Phase 4 Results DMC

• 2 other identifiers: 20130611150669
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether sitagliptin is effective in preventing the development of new-onset diabetes after kidney transplant (NODAT). Up to one-third of previously non-diabetic patients develop NODAT after a kidney transplant. Corticosteroids and calcineurin inhibitors are two commonly utilized anti-rejection medications that contribute to diabetes development through multiple mechanisms; including decreased insulin production by the pancreas. Sitagliptin is an oral medication that results in increased insulin secretion. We hypothesize that administration of sitagliptin to transplant recipients identified to be at risk for diabetes development will reduce the incidence and severity of NODAT.

Conditions

Posttransplant Diabetes Mellitus

Keywords

diabetes; transplant; kidney

Outcome Measures

Primary Outcomes (1)

• 2-hour Oral Glucose Tolerance Test-derived Blood Sugar

  Change in 2-hour OGTT-derived blood sugar will be measured at three months and again at six months. These are 3 month OGTT results

  3 months

Secondary Outcomes (2)

• Normal 2-hour Oral Glucose Tolerance Test-derived Blood Sugar

  3 months

• 6 Month OGTT Result (Completion of Washout From Study Drug)

  6 months

Other Outcomes (2)

• Hemoglobin A1c, 3 Month

  3 months

• Hemoglobin A1c, 6 Month

  6 months

Study Arms (2)

Sitagliptin

ACTIVE COMPARATOR

Sitaglipitin tablets will be administered orally for 3 months from randomization Initial dose will be 100mg/daily, adjusted per renal function: Creatinine clearance \> or = 50mL/min: 100mg/day Creatinine clearance \> or = 30 and \<50mL/min: 50mg/day Creatinine clearance \<30 mL/min or on dialysis: 25mg/day

Drug: Sitagliptin

Placebo

PLACEBO COMPARATOR

Placebo tablets (identical to active comparator in appearance) will be administered orally for 3 months. Starting dose and adjustment based on renal function will be identical to active comparator

Drug: Placebo

Interventions

Sitagliptin DRUG

Also known as: Januvia

Sitagliptin

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (≥18 yo) recipient of living-donor or deceased donor kidney transplant
• Blood sugar ≥ 200 mg/dL in first 72 hours after transplant
• No history of diabetes or prior treatment with insulin or oral hypoglycemic agents

You may not qualify if:

• A1c of ≥6.5% measured immediately pre-transplant
• Recipient of simultaneous kidney-pancreas, kidney-liver, kidney-heart, or kidney-lung transplant
• Prior non-renal solid organ transplant

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

Location

Related Publications (5)

• Yates CJ, Fourlanos S, Hjelmesaeth J, Colman PG, Cohney SJ. New-onset diabetes after kidney transplantation-changes and challenges. Am J Transplant. 2012 Apr;12(4):820-8. doi: 10.1111/j.1600-6143.2011.03855.x. Epub 2011 Nov 28.

  PMID: 22123607 BACKGROUND

• Caillard S, Eprinchard L, Perrin P, Braun L, Heibel F, Moreau F, Kessler L, Moulin B. Incidence and risk factors of glucose metabolism disorders in kidney transplant recipients: role of systematic screening by oral glucose tolerance test. Transplantation. 2011 Apr 15;91(7):757-64. doi: 10.1097/TP.0b013e31820f0877.

  PMID: 21336240 BACKGROUND

• Chakkera HA, Knowler WC, Devarapalli Y, Weil EJ, Heilman RL, Dueck A, Mulligan DC, Reddy KS, Moss AA, Mekeel KL, Mazur MJ, Hamawi K, Castro JC, Cook CB. Relationship between inpatient hyperglycemia and insulin treatment after kidney transplantation and future new onset diabetes mellitus. Clin J Am Soc Nephrol. 2010 Sep;5(9):1669-75. doi: 10.2215/CJN.09481209. Epub 2010 Jun 17.

  PMID: 20558559 BACKGROUND

• Herman GA, Bergman A, Stevens C, Kotey P, Yi B, Zhao P, Dietrich B, Golor G, Schrodter A, Keymeulen B, Lasseter KC, Kipnes MS, Snyder K, Hilliard D, Tanen M, Cilissen C, De Smet M, de Lepeleire I, Van Dyck K, Wang AQ, Zeng W, Davies MJ, Tanaka W, Holst JJ, Deacon CF, Gottesdiener KM, Wagner JA. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes. J Clin Endocrinol Metab. 2006 Nov;91(11):4612-9. doi: 10.1210/jc.2006-1009. Epub 2006 Aug 15.

  PMID: 16912128 BACKGROUND

• 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.

  PMID: 22067216 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: Rowena Delos Santos
• Organization: Washington University in St. Louis

delossantos@wustl.edu

314-362-8351

Study Officials

• Rowena Delos Santos, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2013
• First Posted: August 23, 2013
• Study Start: September 1, 2013
• Primary Completion: June 1, 2020
• Study Completion: October 1, 2020
• Last Updated: December 30, 2022
• Results First Posted: June 29, 2021

Record last verified: 2022-12

Locations

US (1)