Pre Diabetes
Conditions
Keywords
Kidney Transplant
Brief summary
Researchers are trying to determine if an anti-diabetes medication, called Exenatide SR, is well tolerated in kidney transplant patients with elevated blood glucose levels, and if it's effective in preventing diabetes.
Detailed description
New diabetes can develop after transplant and may affect a transplanted kidney's health and a recipient's overall health. Currently, patients who are pre-diabetic are encouraged to exercise and lose weight. Researchers are planning to test whether an addition of this medication will lead to better results and more effectively prevent diabetes in patients who already have high blood sugars. Exenatide SR is medication given by weekly injection. It increases insulin release in response to a meal and slows digestion. This medicine is already in use and approved by the US Food and Drug Administration (FDA) in patients with diabetes. However, it has not been approved for this indication; the FDA has allowed the use of this drug in this research study.
Interventions
DRUGExenatide SR
Exenatide SR 2 mg subcutaneous (SQ) weekly
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Recipients of solitary kidney transplants (i.e. not combined liver-kidney, pancreas-kidney etc.) * At 4 months after transplantation: Prediabetes (fasting blood glucose 100-125 mg/dl; or 2 hr glucose 140-199 or HgbA1c 5.7-6.4%)
Exclusion criteria
* Diabetes pre-transplantation * Diabetes at 4 months * \<18 years of age * eGFR \<30 ml/min (estimated by MDRD equation from serum creatinine) * Active acute cellular rejection including borderline (If treated and resolved, these patients can be included) * BK nephropathy active * History of pancreatitis, pre-existing moderate-to-severe gastroparesis, liver cirrhosis or family /personal history of multiple endocrine neoplasia 2 or medullary thyroid cancer * Pregnant or breastfeeding women. Female Subject must be either: * Of non-child bearing potential: Post-menopausal (defined as at least 1 year without any menses) prior to screening , or documented surgically sterile or status post-hysterectomy * Or if childbearing potential, agree not to try and become pregnant during the study for at least 90 days after the final study drug administration. And have a negative serum or urine pregnancy test. And if heterosexually active, agree to consistently use two forms of highly effective birth control. * Hypersensitivity to Exenatide
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression From Prediabetes to Diabetes | 12 months after transplantation | Number of subjects to have an increase in HbA1C or fasting blood sugar to diabetic range based on the American Diabetes Association (ADA) criteria after kidney transplantation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression From Prediabetes to Diabetes | 24 months after transplantation | Number of subjects to have an increase in HbA1C or fasting blood sugar to diabetic range based on the American Diabetes Association (ADA) criteria after kidney transplantation |
| Creatinine | From enrollment, up to 20 months post-enrollment | A creatinine blood test measures the level of creatinine in the blood. Creatinine is a waste product that forms when creatine, which is found in the muscle, breaks down. Creatinine levels in the blood can provide the doctors with information about how well the kidneys are working. As measured in mg/dL units. |
| Hemoglobin A1c | 12 and 24 months after kidney transplantation | Hemoglobin is a protein within red blood cells. As glucose enters the bloodstream, it binds to hemoglobin, or glycates. The more glucose that enters the bloodstream, the higher the amount of glycated hemoglobin. An A1C level below 5.7 percent is considered normal. |
| Incidence of Death | From enrollment, up to 20 months post-enrollment | Number of subjects to experience death by any cause |
| Graft Loss | From enrollment, up to 20 months post-enrollment | The number of subjects to experience graft loss. Primary graft failure is defined as no evidence of engraftment or hematological recovery of donor cells, within the first month after transplant, without evidence of disease relapse. Secondary graft failure refers to the loss of a previously functioning graft, resulting in cytopenia involving at least two blood cell lineages. |
| Adverse Events for Exenatide SR Intervention | 12 months | Total number of adverse events reported by the subjects that received the Exenatide SR Intervention |
| Incidence of Mesangial Expansion | 12 and 24 months after kidney transplantation | Number of subjects to experience mesangial expansion \>20%. Mesangial expansion occurs due to increased deposition of extracellular matrix proteins, for example fibronectin, into the mesangium. Accumulation of extracellular matrix proteins then occurs due to insufficient degradation by matrix metalloproteinases. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exenatide SR Intervention Group Subjects received, in addition to standard care, Exenatide SR 2 mg subcutaneous (SQ) weekly for 24 months.
Exenatide SR: Exenatide SR 2 mg subcutaneous (SQ) weekly | 6 |
| Standard of Care Subjects received standard post-transplant care as per Mayo Clinic usual practice. | 3 |
| Total | 9 |
Baseline characteristics
| Characteristic | Exenatide SR Intervention Group | Total | Standard of Care |
|---|---|---|---|
| Age, Continuous | 48.5 years | 53.5 years | 57.7 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 6 Participants | 9 Participants | 3 Participants |
| Region of Enrollment United States | 6 participants | 9 participants | 3 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 4 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Progression From Prediabetes to Diabetes
Number of subjects to have an increase in HbA1C or fasting blood sugar to diabetic range based on the American Diabetes Association (ADA) criteria after kidney transplantation
Time frame: 12 months after transplantation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Exenatide SR Intervention Group | Progression From Prediabetes to Diabetes | 0 Participants |
| Standard of Care | Progression From Prediabetes to Diabetes | 1 Participants |
Secondary
Adverse Events for Exenatide SR Intervention
Total number of adverse events reported by the subjects that received the Exenatide SR Intervention
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide SR Intervention Group | Adverse Events for Exenatide SR Intervention | 10 Adverse Events |
Secondary
Creatinine
A creatinine blood test measures the level of creatinine in the blood. Creatinine is a waste product that forms when creatine, which is found in the muscle, breaks down. Creatinine levels in the blood can provide the doctors with information about how well the kidneys are working. As measured in mg/dL units.
Time frame: From enrollment, up to 20 months post-enrollment
Population: Data was not collected nor analyzed for one subject in the standard of care arm
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exenatide SR Intervention Group | Creatinine | 1.7 mg/dL |
| Standard of Care | Creatinine | 1.4 mg/dL |
Secondary
Graft Loss
The number of subjects to experience graft loss. Primary graft failure is defined as no evidence of engraftment or hematological recovery of donor cells, within the first month after transplant, without evidence of disease relapse. Secondary graft failure refers to the loss of a previously functioning graft, resulting in cytopenia involving at least two blood cell lineages.
Time frame: From enrollment, up to 20 months post-enrollment
Population: Graft loss collected for the Exenatide SR Intervention Group only. Graft Loss was not collected for the Standard of Care arm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Exenatide SR Intervention Group | Graft Loss | 0 Participants |
Secondary
Hemoglobin A1c
Hemoglobin is a protein within red blood cells. As glucose enters the bloodstream, it binds to hemoglobin, or glycates. The more glucose that enters the bloodstream, the higher the amount of glycated hemoglobin. An A1C level below 5.7 percent is considered normal.
Time frame: 12 and 24 months after kidney transplantation
Population: Data was not collected nor analyzed for one subject in the standard of care arm
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Exenatide SR Intervention Group | Hemoglobin A1c | 12 months | 5.6 percentage of glycated hemoglobin |
| Exenatide SR Intervention Group | Hemoglobin A1c | 24 months | 5.65 percentage of glycated hemoglobin |
| Standard of Care | Hemoglobin A1c | 12 months | 5.85 percentage of glycated hemoglobin |
| Standard of Care | Hemoglobin A1c | 24 months | 5.75 percentage of glycated hemoglobin |
Secondary
Incidence of Death
Number of subjects to experience death by any cause
Time frame: From enrollment, up to 20 months post-enrollment
Population: Deaths collected for the Exenatide SR Intervention Group only. Deaths were not collected for the Standard of Care arm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Exenatide SR Intervention Group | Incidence of Death | 0 Participants |
Secondary
Incidence of Mesangial Expansion
Number of subjects to experience mesangial expansion \>20%. Mesangial expansion occurs due to increased deposition of extracellular matrix proteins, for example fibronectin, into the mesangium. Accumulation of extracellular matrix proteins then occurs due to insufficient degradation by matrix metalloproteinases.
Time frame: 12 and 24 months after kidney transplantation
Population: Data was not collected nor analyzed for one subject in the standard of care arm at 24 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Exenatide SR Intervention Group | Incidence of Mesangial Expansion | 12 months | 0 Participants |
| Exenatide SR Intervention Group | Incidence of Mesangial Expansion | 24 months | 0 Participants |
| Standard of Care | Incidence of Mesangial Expansion | 12 months | 0 Participants |
| Standard of Care | Incidence of Mesangial Expansion | 24 months | 0 Participants |
Secondary
Progression From Prediabetes to Diabetes
Number of subjects to have an increase in HbA1C or fasting blood sugar to diabetic range based on the American Diabetes Association (ADA) criteria after kidney transplantation
Time frame: 24 months after transplantation
Population: Data was not collected nor analyzed for one subject in the standard of care arm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Exenatide SR Intervention Group | Progression From Prediabetes to Diabetes | 1 Participants |
| Standard of Care | Progression From Prediabetes to Diabetes | 1 Participants |