A Clinical Trial to Prevent New Onset Diabetes After Transplantation (ITP-NODAT)

Specific Aim 1: To determine the clinical efficacy of early initiation of insulin therapy in decreasing the incidence of NODAT among de novo kidney transplant patients with manifested post-transplant hyperglycemia during the first week after transplantation.

Hypothesis 1: Early initiation of insulin therapy protects beta-cell from early stress related to the surgery and use of higher doses of immunosuppressive medications, and leads to lower incidence of NODAT at 1 and 2 years.

Specific Aim 2: To determine the improvement in overall glycemic control with the early initiation of insulin therapy.

Hypothesis 2: Early initiation of insulin therapy results in greater overall control of glycemia compared to standard care of dietary counseling, life-style modification, oral hypoglycemic agents and/or insulin as needed at 1 year.

Specific Aim 3: To determine the improvement in beta-cell function among patients assigned to the early initiation of insulin therapy at one year post-transplantation.

Hypothesis 3: Early initiation of insulin therapy protects beta-cell from glucotoxicity of post-transplant hyperglycemia and preserves better beta-cell function at 1 year.

Study Overview

• Status: Completed
• Conditions: Prevention of New Onset Diabetes Among Kidney Transplant Patients
• Intervention / Treatment: Drug: Insulin treatment for hyperglycemia

• Study Type: Interventional
• Enrollment (Actual): 251
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

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:

1. Adult patients (> 18 years) with end stage renal disease (ESRD) undergoing kidney transplantation;
2. Standard triple immunosuppressive medications following kidney transplantation including tacrolimus, mycophenolate mofetil and corticosteroids;
3. Capable to understand the study protocol and to give informed consent;

Exclusion Criteria:

1. Type 1 and 2 Diabetes Mellitus (DM) either as co-morbidity or cause of ESRD;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Insulin treatment for hyperglycemia; Neutral Protamine Hagedorn (NPH) Insulin Titration Regimen, based on pre-dinner capillary blood glucose measurements (CPG) expressed in mg/dl; All NPH initiation doses and dose adjustments are presented in IU/day For pts. with CPG > 240, NPH initiation: 14, dose increases by 4; For pts. with CPG > 180 mg/dl, NPH initiation: 12, dose increases by 4; For pts. with CPG > 140 mg/dl, NPH initiation: 10, dose increases by 4; For pts. with CPG > 120 mg/dl, NPH initiation: 0, dose increases by 2; For pts. with CPG 100-119 mg/dl, NPH initiation: 0, maintain dose; For pts. with CPG 80-<100 mg/dl, NPH initiation: 0, dose decrease by 4; For pts. with CPG 60-<80 mg/dl, NPH initiation: 0, decrease by 8; For pts. with CPG <60 mg/dl, NPH initiation: 0, ½ of previous dose.	Drug: Insulin treatment for hyperglycemia
No Intervention: Standard of care; Patients assigned in this arm will receive standard of care following their kidney transplantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Incidence of New Onset of Diabetes After Transplant (NODAT) 12 Months After Kidney Transplantation	NODAT will be defined according to American Diabetes Association definition: Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or; 2 hours Oral Glucose Tolerance Test (OGTT) values equal or greater than 200 mg/dl; and/or; Glycosylated hemoglobin A1c equal or greater than 6.5; and/or; On oral hypoglycemic agents and/or insulin therapy; Incidence is measured in terms of number of participants who meet any of these 4 criteria.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Incidence of New Onset of Diabetes After Transplant (NODAT) 24 Months After Kidney Transplantation	NODAT will be defined according to American Diabetes Association definition: Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or; 2 hours OGTT values equal or greater than 200 mg/dl; and/or; Glycosylated hemoglobin A1c equal or greater than 6.5; and/or; On oral hypoglycemic agents and/or insulin therapy;	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Impaired Fasting Glycemia and Impaired Glucose Tolerance 6, 12 and 24 Months After Transplantation.	Following American Diabetes Association's definition: Impaired fasting glycemia: fasting glucose levels between 100 and 125 mg/dl; Impaired glucose tolerance: 2 hours' OGTT values between 140 and 199 mg/dl;	6, 12 and 24 months

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2012
• Primary Completion (Actual): February 27, 2018
• Study Completion (Actual): February 27, 2018

Study Registration Dates

• First Submitted: August 30, 2012
• First Submitted That Met QC Criteria: September 6, 2012
• First Posted (Estimate): September 11, 2012

Study Record Updates

• Last Update Posted (Actual): March 20, 2019
• Last Update Submitted That Met QC Criteria: February 26, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Insulin; Prevention; Kidney transplant; New onset diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: 1R01DK092475-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes