Prevention of New Onset Diabetes Among Kidney Transplant Patients
Conditions
Keywords
Kidney transplant, New onset diabetes, Prevention, Insulin
Brief summary
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.
Interventions
DRUGInsulin treatment for hyperglycemia
Sponsors
Medical University of Vienna
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of New Onset of Diabetes After Transplant (NODAT) 12 Months After Kidney Transplantation | 12 months | NODAT will be defined according to American Diabetes Association definition: 1. Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or 2. 2 hours Oral Glucose Tolerance Test (OGTT) values equal or greater than 200 mg/dl; and/or 3. Glycosylated hemoglobin A1c equal or greater than 6.5; and/or 4. On oral hypoglycemic agents and/or insulin therapy; Incidence is measured in terms of number of participants who meet any of these 4 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of New Onset of Diabetes After Transplant (NODAT) 24 Months After Kidney Transplantation | 24 months | NODAT will be defined according to American Diabetes Association definition: 1. Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or 2. 2 hours OGTT values equal or greater than 200 mg/dl; and/or 3. Glycosylated hemoglobin A1c equal or greater than 6.5; and/or 4. On oral hypoglycemic agents and/or insulin therapy; |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Impaired Fasting Glycemia and Impaired Glucose Tolerance 6, 12 and 24 Months After Transplantation. | 6, 12 and 24 months | 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; |
Countries
United States
Participant flow
Pre-assignment details
Of 42 participants randomized prior to kidney transplantation at University of Michigan, 6 did not undergo study procedure due to medical conditions that developed in the immediate postoperative period which prevented them from going forward in the study. Data are not available on the 209 participants randomized through the University of Austria.
Participants by arm
| Arm | Count |
|---|---|
| Insulin Treatment for Hyperglycemia 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. | 18 |
| Standard of Care Patients assigned in this arm will receive standard of care following their kidney transplantation. | 18 |
| Total | 36 |
Baseline characteristics
| Characteristic | Insulin Treatment for Hyperglycemia | Total | Standard of Care |
|---|---|---|---|
| Age, Continuous | 52.6 years STANDARD_DEVIATION 13.9 | 48.6 years STANDARD_DEVIATION 15.1 | 44.6 years STANDARD_DEVIATION 15.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 33 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 29 Participants | 16 Participants |
| Region of Enrollment United States | 18 participants | 36 participants | 18 participants |
| Sex: Female, Male Female | 10 Participants | 20 Participants | 10 Participants |
| Sex: Female, Male Male | 8 Participants | 16 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 15 / 18 | 14 / 18 |
| serious Total, serious adverse events | 15 / 18 | 10 / 18 |
Outcome results
Primary
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: 1. Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or 2. 2 hours Oral Glucose Tolerance Test (OGTT) values equal or greater than 200 mg/dl; and/or 3. Glycosylated hemoglobin A1c equal or greater than 6.5; and/or 4. On oral hypoglycemic agents and/or insulin therapy; Incidence is measured in terms of number of participants who meet any of these 4 criteria.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin Treatment for Hyperglycemia | The Incidence of New Onset of Diabetes After Transplant (NODAT) 12 Months After Kidney Transplantation | 3 Participants |
| Standard of Care | The Incidence of New Onset of Diabetes After Transplant (NODAT) 12 Months After Kidney Transplantation | 1 Participants |
p-value: 0.8795% CI: [1.01, 1.06]Chi-squared
Secondary
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: 1. Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or 2. 2 hours OGTT values equal or greater than 200 mg/dl; and/or 3. Glycosylated hemoglobin A1c equal or greater than 6.5; and/or 4. On oral hypoglycemic agents and/or insulin therapy;
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin Treatment for Hyperglycemia | The Incidence of New Onset of Diabetes After Transplant (NODAT) 24 Months After Kidney Transplantation | 1 Participants |
| Standard of Care | The Incidence of New Onset of Diabetes After Transplant (NODAT) 24 Months After Kidney Transplantation | 0 Participants |
p-value: 0.9295% CI: [1.2, 2.8]Chi-squared
Other Pre-specified
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;
Time frame: 6, 12 and 24 months