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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01928199
Recruitment Status : Active, not recruiting
First Posted : August 23, 2013
Last Update Posted : January 21, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Rowena Delos Santos, Washington University School of Medicine

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.

Condition or disease Intervention/treatment Phase
Posttransplant Diabetes Mellitus Drug: Sitagliptin Drug: Placebo Phase 4

Detailed Description:

This will be a single-center, randomized, double-blind trial to evaluate the efficacy of sitagliptin to prevent the development of new-onset diabetes after transplant (NODAT) in previously non-diabetic patients with post-operative hyperglycemia following living-donor or deceased-donor kidney transplant. In this trial, previously non-diabetic adult patients with hyperglycemia (random blood sugar >200mg/dL) in the first 72 hours following kidney transplant will be screened to determine eligibility based on inclusion/exclusion criteria. Patients that meet study entry criteria will be stratified based on HbA1c (<5.7 or 5.7-6.4%) and randomized in a 1:1 ratio to one of two treatment groups: sitagliptin versus placebo. Fifty patients (25 per group) will be enrolled. Dosing period will be 3 months at which time study drug will be discontinued and patients will be followed for an additional 3 month period.

Study visits will occur at 0, 1, 3 and 6 months. A HbA1c and 2-hour oral glucose tolerance test (OGTT) will be obtained at the 3 and 6 month study visit.

Screening period (Visit 1)

All patients presenting for living-donor or deceased donor kidney transplant will have a medical history, medication history, vital signs, height, weight, body mass index, physical exam, random blood sugar (BS), HbA1c and EKG done as part of routine pre-transplant protocol at Barnes Jewish Hospital. Patients with hyperglycemia, defined as a random blood sugar ≥ 200 mg/dL, in the first 72 hours after kidney transplant will be screened to determine eligibility for the study based on inclusion and exclusion criteria.

Randomization (Visit 2)

Patients meeting study entry criteria and consenting to study participation will be stratified based on HbA1c (<5.7 or 5.7-6.4%) and block randomized in blocks of eight in a 1:1 ratio to sitagliptin versus placebo. Sitagliptin dose will be 100mg/day, adjusted per creatinine clearance and tolerability. Patients will be instructed by a licensed diabetic educator on proper measurement and recording of fasting and post-prandial blood sugars. Subjects will be provided a log, standard glucometer and testing strips to maintain a blood sugar log post-discharge. Visit 2 will occur within 24 hours after Visit 1.

Drug dosing period (Visits 3-4)

Sitagliptin or placebo will be continued until 3 months post-transplant, at which time study medication will be discontinued and collected from the subject. At the 1 and 3 month visits, vital signs, height, weight, and BMI will be obtained. A physical exam will be performed. Blood sugar logs provided by the patient will be reviewed and adverse effects recorded. At the 3 month visit (Visit 4), a HbA1c, 2-hour OGTT, fasting C-peptide and insulin level will be obtained.

Follow-up (Visit 5)

At the 6 month final visit, 3 months following discontinuation of study medication, vital signs, height, weight, BMI, HbA1c, 2-hour OGTT, fasting C-peptide and insulin level will be obtained. A physical exam will be performed. Blood sugar logs provided by the patient will be reviewed and adverse effects recorded.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Single Center, Randomized, Double-blind Controlled Trial of Sitagliptin Versus Placebo to Reduce the Incidence and Severity of New-onset Diabetes After Kidney Transplant
Study Start Date : September 2013
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Sitagliptin

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
Other Name: Januvia

Placebo Comparator: Placebo
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



Primary Outcome Measures :
  1. 2-hour oral glucose tolerance test-derived blood sugar [ Time Frame: 3 months ]
    Change in 2-hour OGTT-derived blood sugar will be measured from three months to six months


Secondary Outcome Measures :
  1. Normal 2-hour oral glucose tolerance test-derived blood sugar [ Time Frame: 3 months ]
    Number of subjects who have normal 2-hour oral glucose tolerance test-derived blood sugar will be measured at 3 months



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

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): NCT01928199


Locations
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United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Rowena Delos Santos, MD Washington University School of Medicine
Publications:

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Responsible Party: Rowena Delos Santos, Assistant Professor of Medicine, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01928199    
Other Study ID Numbers: 201306111
50669 ( Other Grant/Funding Number: Merck )
First Posted: August 23, 2013    Key Record Dates
Last Update Posted: January 21, 2020
Last Verified: January 2020
Keywords provided by Rowena Delos Santos, Washington University School of Medicine:
diabetes
transplant
kidney
Additional relevant MeSH terms:
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Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System 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