Diabetes, Pancreatitis
Conditions
Keywords
Pancreatitis, Pancreatectomy, Islet autotransplant, Sitagliptin, Diabetes
Brief summary
The purpose of the study is to test the effects of sitagliptin on the need for insulin (the hormone that lowers blood sugars) by patients who receive a pancreatectomy and islet autotransplant for chronic pancreatitis.
Detailed description
At the current time, about one-third of patients are insulin independent (do not need to take insulin) after autotransplant, but the other two-thirds still need some insulin. Sitagliptin works by increasing the amount of a hormone called glucagon-like peptide 1, or GLP-1, in the body which then increases the amount of insulin that is made by the beta cells(the insulin producing cell of the islets). GLP-1 might also help protect beta cells from dying under stressful conditions and increase the production of new beta cells. The primary goal of this study is to see if taking sitagliptin for one year after islet autotransplant increases the number of patients who achieve and maintain insulin independence. Other goals of this study are to see if sitagliptin reduces the amount of insulin injections needed or helps the islets make more insulin.
Interventions
DRUGSitagliptin
100 mg PO daily
DRUGPlacebo
Placebo
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Scheduled for total pancreatectomy and IAT at UM
Exclusion criteria
* Pre-existing diabetes mellitus or hyperglycemia with fasting glucose ≥115 mg/dl * Medical conditions which, in the opinion of the investigator, might impact islet function (e.g asthma or inflammatory disease requiring chronic systemic corticosteroids) * Significant renal disease: serum creatinine levels of \>3.0 mg/dL in men and \>2.5 mg/dL in women, or end-stage renal disease requiring hemodialysis or peritoneal dialysis. * For female subjects, plans to become pregnant or unwillingness to practice birth control for 18 months. * Islet yield \<1,000 IE/kg body weight (exclusion for treatment with drug/placebo)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Independence | 12 months | percentage of patients insulin independent |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Independence | 18 months | percentage of patients insulin independent |
| Area Under the Curve (AUC) C-peptide (ng/dL*Min) | 12 months | AUC C-peptide obtained from a mixed meal test (measured time 0 to 2 hours after Boost HP) |
| AUC C-peptide | 18 months | AUC C-peptide (ng/dL\*min) from mixed meal tolerance test (measured times 0 to 2 hours after Boost HP) |
| Acute C-peptide Response (ACR) to Glucose | 12 months | Derived from intravenous gluocose tolerance testing (0 to 10 minute measures after dextrose bolus) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin Sitagliptin: 100 mg PO daily | 54 |
| Placebo Placebo: Placebo | 29 |
| Total | 83 |
Baseline characteristics
| Characteristic | Sitagliptin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 39.0 years STANDARD_DEVIATION 11 | 42.6 years STANDARD_DEVIATION 10.3 | 41 years STANDARD_DEVIATION 11 |
| Region of Enrollment United States | 54 participants | 29 participants | 83 participants |
| Sex: Female, Male Female | 44 Participants | 23 Participants | 67 Participants |
| Sex: Female, Male Male | 10 Participants | 6 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 54 / 54 | 29 / 29 |
| serious Total, serious adverse events | 31 / 54 | 26 / 29 |
Outcome results
Primary
Insulin Independence
percentage of patients insulin independent
Time frame: 12 months
Population: N's reflect patients that returned for study follow up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Insulin Independence | 42 percentage of participants |
| Placebo | Insulin Independence | 45 percentage of participants |
Secondary
Acute C-peptide Response (ACR) to Glucose
Derived from intravenous gluocose tolerance testing (0 to 10 minute measures after dextrose bolus)
Time frame: 12 months
Population: This test required two IVs. In patients for whom 2 IVs could not be placed successfully, this test could not be performed. N's reflect number of patients completing this test.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Acute C-peptide Response (ACR) to Glucose | 9.9 min*ng/dL | Standard Error 1.2 |
| Placebo | Acute C-peptide Response (ACR) to Glucose | 7.2 min*ng/dL | Standard Error 1.6 |
Secondary
Acute C-peptide Response (ACR) to Glucose
Derived from intravenous glucose tolerance test (0 to 10 minute measures after IV dextrose bolus)
Time frame: 18 months
Population: This test required two IVs. In patients for whom 2 IVs could not be placed successfully, this test could not be performed. N's reflect number of patients completing this test.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Acute C-peptide Response (ACR) to Glucose | 6.9 min*ng/dL | Standard Error 1 |
| Placebo | Acute C-peptide Response (ACR) to Glucose | 6.0 min*ng/dL | Standard Error 1.4 |
Secondary
Area Under the Curve (AUC) C-peptide (ng/dL*Min)
AUC C-peptide obtained from a mixed meal test (measured time 0 to 2 hours after Boost HP)
Time frame: 12 months
Population: Patients with vomiting, NPO restrictions (due to chronic GI illness) were not able to complete MMTT. The N for each group reflects the number of patients who successfully completed this assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Area Under the Curve (AUC) C-peptide (ng/dL*Min) | 273 ng*min/dL | Standard Error 20 |
| Placebo | Area Under the Curve (AUC) C-peptide (ng/dL*Min) | 273 ng*min/dL | Standard Error 27 |
Secondary
AUC C-peptide
AUC C-peptide (ng/dL\*min) from mixed meal tolerance test (measured times 0 to 2 hours after Boost HP)
Time frame: 18 months
Population: Patients with vomiting, NPO (Nothing by Mouth) restrictions (due to chronic GI illness) were not able to complete MMTT. (Mixed meal Tolerance Test) The N for each group reflects the number of patients who successfully completed this assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | AUC C-peptide | 274 min*ng/dL | Standard Deviation 20 |
| Placebo | AUC C-peptide | 235 min*ng/dL | Standard Deviation 27 |
Secondary
Insulin Independence
percentage of patients insulin independent
Time frame: 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Insulin Independence | 36 percentage of participants |
| Placebo | Insulin Independence | 44 percentage of participants |