A Clinical Trial to Prevent New Onset Diabetes After Transplantation

Study Overview
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Brief Summary
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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.

Official Title
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A Clinical Trial to Prevent New Onset Diabetes After Transplantation

Conditions
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Prevention of New Onset Diabetes Among Kidney Transplant Patients

Intervention / Treatment
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* Drug: Insulin treatment for hyperglycemia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (> 18 years) with end stage renal disease (ESRD) undergoing kidney transplantation; Standard triple immunosuppressive medications following kidney transplantation including tacrolimus, mycophenolate mofetil and corticosteroids; 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;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Insulin treatment for hyperglycemia<br>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<br> <br> |
| No Intervention: Standard of care<br>Patients assigned in this arm will receive standard of care following their kidney transplantation. | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney transplant, New onset diabetes, Prevention, Insulin