Chronic Pancreatitis, Diabetes Mellitus
Conditions
Keywords
Total Pancreatectomy, Islet Auto-Transplantation, Closed Loop Insulin Pump
Brief summary
The purpose of this study is to determine the effectiveness of closed loop insulin pump therapy to control blood sugar following total pancreatectomy and islet auto-transplantation (TPIAT).
Detailed description
OBJECTIVES AND HYPOTHESES The main objective of this study is to determine if a closed loop insulin system can successfully achieve tighter blood sugar control than the current multiple daily injection regimen. The investigators hypothesize that the average blood glucose will be lower in the closed loop group than the control group, there will be less glucose variability in the closed loop group than the control group, and there will be less total time spent in hyperglycemia and hypoglycemia in the closed loop group than in the control group. The investigators also will investigate insulin requirements and islet function in the first 6 months post-transplant in the closed loop group The investigators hypothesize that the insulin requirements will be lower and the C-peptide levels higher in the closed loop group than in the control group.
Interventions
DEVICEClosed Loop Insulin
The Closed Loop Insulin system is an automated insulin delivery system based on body blood glucose. It consists of an Insulin pump, continuous glucose monitor, and a control device (laptop with algorithms).
Sponsors
Medtronic Diabetes
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Patients undergoing total pancreatectomy and islet auto-transplantation. * Patients ages 21 to 64 years old
Exclusion criteria
* Preexisting diabetes * Use of acetaminophen during study period, which interferes with CGM sensor function * Any medical condition requiring corticosteroids * Severe Psychiatric disease or developmental delays, that might interfere with the ability to provide informed consent * Any other medical condition which in the opinion of the investigators impairs the person's ability to safely participate in the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Study Period: Average Serum BG | 3 days of investigation period | Mean blood glucose value: a single report of the average of the analytical blood glucose values will be computed and compared between the pump and control groups. |
| Study Period: Serum BG Standard Deviation | 3 days of investigation period | Measure of glycemic variability. This is the standard deviation in all serum BG values for each individual patient. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study Period: Percent Time BG in Range 70-140 mg/dL | continuous over the 72 hour investigation period | Additional measure of glycemic variability, as reflected by CGM measures, % time in the range of 70-140 on CGM |
| Study Period: CGM Area Under the Curve (AUC) With Glucose < 70 mg/dL | continuous over the 72 hour investigation period | Calculated as the area under the curve on the CGM tracing that the glucose is under 70 mg/dL. |
| Study Period: % of Time CGM BG <70 mg/dL | continuous over the 72 hour investigation period | — |
| Study Period: CGM AUC With Glucose> 140 mg/dL | continuous over the 72 hour investigation period | — |
| Study Period: % of Time CGM BG > 140 mg/dL | continuous over the 72 hour investigation period | — |
| Study Period: Continuous Glucose Monitor (CGM) BG Average | continuously over the 72 hour investigational period | Continuous glucose monitoring sensor data: The CGM's in the pump and control groups will collect glucose readings continuously over a 72 hour period |
| Study Period: Daily Insulin Needs | Average of 3 day study period | Calculated as total daily dose of insulin. |
| Day 14 Follow-Up: Average Serum BG | Day 14 Follow-Up | — |
| Day 14 Follow-Up: C-Peptide | Day 14 Follow-Up: | — |
| Day 28 Follow-Up: Average Serum BG | Day 28 Follow-Up | — |
| Day 28 Follow-Up: C-Peptide | Day 28 Follow-Up | — |
| Study Period: Morning C-peptide | Average of 3 day study period | A single C-peptide measurement collected daily x 3 days, collected at random (meaning not in a fasting state) each morning. Expressed as average for each patient. |
| Study Period: Continuous Glucose Monitor Standard Deviation of BG | continuous over the 72 hour investigation period | measure of glycemic variability by CGM. This is the standard deviation within each patient for all CGM glucose readings. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Control Group: patients receive conventional multiple daily injection insulin therapy with basal and bolus dosing during the 72 hour study period. | 7 |
| Closed Loop Insulin Closed Loop Insulin Group: patients receive continuous subcutaneous insulin controlled by experimental closed loop system during the 72 hour study period.
Closed Loop Insulin: The Closed Loop Insulin system is an automated insulin delivery system based on body blood glucose. It consists of an Insulin pump, continuous glucose monitor, and a control device (laptop with algorithms). | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | Total | Control | Closed Loop Insulin |
|---|---|---|---|
| Age, Continuous | 35.9 years STANDARD_DEVIATION 11.4 | 33.1 years STANDARD_DEVIATION 13.3 | 38.6 years STANDARD_DEVIATION 9.4 |
| Body Mass Index (BMI) at Transplant | 25.1 kg/m2 STANDARD_DEVIATION 4.9 | 24.9 kg/m2 STANDARD_DEVIATION 5.7 | 25.3 kg/m2 STANDARD_DEVIATION 4.5 |
| Days on drip | 6.0 days STANDARD_DEVIATION 1.4 | 6.9 days STANDARD_DEVIATION 1.1 | 5.1 days STANDARD_DEVIATION 1.1 |
| Etiology of Chronic Pancreatitis (CP) Identified Genetic Mutation (PRSS1, SPINK1, CFTR) | 4 participants | 1 participants | 3 participants |
| Etiology of Chronic Pancreatitis (CP) Idiopathic Pancreatitis | 3 participants | 2 participants | 1 participants |
| Etiology of Chronic Pancreatitis (CP) Mechanical Dysfunction | 7 participants | 4 participants | 3 participants |
| Fasting Blood Glucose (BG) | 92 mg/dL STANDARD_DEVIATION 10.3 | 95 mg/dL STANDARD_DEVIATION 13 | 89 mg/dL STANDARD_DEVIATION 6 |
| Fasting C-Peptide | 92 ng/mL STANDARD_DEVIATION 10.3 | 95 ng/mL STANDARD_DEVIATION 13 | 89 ng/mL STANDARD_DEVIATION 6 |
| hemoglobin A1c (A1c) | 5.3 % STANDARD_DEVIATION 0.4 | 5.4 % STANDARD_DEVIATION 0.5 | 5.1 % STANDARD_DEVIATION 0.2 |
| Islet Yield | 5432 IEq/kg STANDARD_DEVIATION 2983 | 4245 IEq/kg STANDARD_DEVIATION 2174 | 6619 IEq/kg STANDARD_DEVIATION 3357 |
| Peak Mixed Meal Tolerance Test (MMTT) C-peptide | 6.1 ng/mL STANDARD_DEVIATION 3.4 | 5.8 ng/mL STANDARD_DEVIATION 4.4 | 6.4 ng/mL STANDARD_DEVIATION 2.2 |
| Sex: Female, Male Female | 9 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 1 Participants |
| Weight at Transplant | 71.4 kg STANDARD_DEVIATION 18.4 | 76.7 kg STANDARD_DEVIATION 23.7 | 66.1 kg STANDARD_DEVIATION 10.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 7 | 3 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
Primary
Study Period: Average Serum BG
Mean blood glucose value: a single report of the average of the analytical blood glucose values will be computed and compared between the pump and control groups.
Time frame: 3 days of investigation period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Study Period: Average Serum BG | 130 mg/dL | Standard Deviation 13 |
| Closed Loop Insulin | Study Period: Average Serum BG | 111 mg/dL | Standard Deviation 4 |
p-value: 0.003t-test, 2 sided
Primary
Study Period: Serum BG Standard Deviation
Measure of glycemic variability. This is the standard deviation in all serum BG values for each individual patient.
Time frame: 3 days of investigation period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Study Period: Serum BG Standard Deviation | 21.0 mg/dL | Standard Deviation 10.2 |
| Closed Loop Insulin | Study Period: Serum BG Standard Deviation | 14.1 mg/dL | Standard Deviation 3.3 |
p-value: 0.115t-test, 2 sided
Secondary
Day 14 Follow-Up: Average Serum BG
Time frame: Day 14 Follow-Up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Day 14 Follow-Up: Average Serum BG | 135 mg/dL | Standard Deviation 81 |
| Closed Loop Insulin | Day 14 Follow-Up: Average Serum BG | 106 mg/dL | Standard Deviation 16 |
p-value: 0.401t-test, 2 sided
Secondary
Day 14 Follow-Up: C-Peptide
Time frame: Day 14 Follow-Up:
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Day 14 Follow-Up: C-Peptide | 1.0 ng/mL | Standard Deviation 0.9 |
| Closed Loop Insulin | Day 14 Follow-Up: C-Peptide | 1.6 ng/mL | Standard Deviation 0.9 |
p-value: 0.22t-test, 2 sided
Secondary
Day 28 Follow-Up: Average Serum BG
Time frame: Day 28 Follow-Up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Day 28 Follow-Up: Average Serum BG | 113 mg/dL | Standard Deviation 29 |
| Closed Loop Insulin | Day 28 Follow-Up: Average Serum BG | 100 mg/dL | Standard Deviation 21 |
p-value: 0.325t-test, 2 sided
Secondary
Day 28 Follow-Up: C-Peptide
Time frame: Day 28 Follow-Up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Day 28 Follow-Up: C-Peptide | 1.0 ng/mL | Standard Deviation 1.2 |
| Closed Loop Insulin | Day 28 Follow-Up: C-Peptide | 1.7 ng/mL | Standard Deviation 1.2 |
p-value: 0.311t-test, 2 sided
Secondary
Study Period: CGM Area Under the Curve (AUC) With Glucose < 70 mg/dL
Calculated as the area under the curve on the CGM tracing that the glucose is under 70 mg/dL.
Time frame: continuous over the 72 hour investigation period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Study Period: CGM Area Under the Curve (AUC) With Glucose < 70 mg/dL | 1615 min*mg/dL/day | Standard Deviation 4267 |
| Closed Loop Insulin | Study Period: CGM Area Under the Curve (AUC) With Glucose < 70 mg/dL | 146 min*mg/dL/day | Standard Deviation 270 |
p-value: 0.38t-test, 2 sided
Secondary
Study Period: CGM AUC With Glucose> 140 mg/dL
Time frame: continuous over the 72 hour investigation period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Study Period: CGM AUC With Glucose> 140 mg/dL | 7860 min*mg/dL/day | Standard Deviation 11444 |
| Closed Loop Insulin | Study Period: CGM AUC With Glucose> 140 mg/dL | 2025 min*mg/dL/day | Standard Deviation 1177 |
p-value: 0.205t-test, 2 sided
Secondary
Study Period: Continuous Glucose Monitor (CGM) BG Average
Continuous glucose monitoring sensor data: The CGM's in the pump and control groups will collect glucose readings continuously over a 72 hour period
Time frame: continuously over the 72 hour investigational period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Study Period: Continuous Glucose Monitor (CGM) BG Average | 125 mg/dL | Standard Deviation 20 |
| Closed Loop Insulin | Study Period: Continuous Glucose Monitor (CGM) BG Average | 114 mg/dL | Standard Deviation 4 |
p-value: 0.193t-test, 2 sided
Secondary
Study Period: Continuous Glucose Monitor Standard Deviation of BG
measure of glycemic variability by CGM. This is the standard deviation within each patient for all CGM glucose readings.
Time frame: continuous over the 72 hour investigation period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Study Period: Continuous Glucose Monitor Standard Deviation of BG | 21.0 mg/dL | Standard Deviation 10.3 |
| Closed Loop Insulin | Study Period: Continuous Glucose Monitor Standard Deviation of BG | 20.1 mg/dL | Standard Deviation 5.1 |
p-value: 0.848t-test, 2 sided
Secondary
Study Period: Daily Insulin Needs
Calculated as total daily dose of insulin.
Time frame: Average of 3 day study period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Study Period: Daily Insulin Needs | 0.56 U/kg/day | Standard Deviation 0.31 |
| Closed Loop Insulin | Study Period: Daily Insulin Needs | 0.26 U/kg/day | Standard Deviation 0.17 |
p-value: 0.04t-test, 2 sided
Secondary
Study Period: Morning C-peptide
A single C-peptide measurement collected daily x 3 days, collected at random (meaning not in a fasting state) each morning. Expressed as average for each patient.
Time frame: Average of 3 day study period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Study Period: Morning C-peptide | 1.6 ng/mL | Standard Deviation 1 |
| Closed Loop Insulin | Study Period: Morning C-peptide | 1.3 ng/mL | Standard Deviation 0.6 |
p-value: 0.443t-test, 2 sided
Secondary
Study Period: % of Time CGM BG > 140 mg/dL
Time frame: continuous over the 72 hour investigation period
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Study Period: % of Time CGM BG > 140 mg/dL | 23.7 % of time |
| Closed Loop Insulin | Study Period: % of Time CGM BG > 140 mg/dL | 9.7 % of time |
p-value: 0.157t-test, 2 sided
Secondary
Study Period: % of Time CGM BG <70 mg/dL
Time frame: continuous over the 72 hour investigation period
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Study Period: % of Time CGM BG <70 mg/dL | 4.8 % of time |
| Closed Loop Insulin | Study Period: % of Time CGM BG <70 mg/dL | 1.1 % of time |
p-value: 0.461t-test, 2 sided
Secondary
Study Period: Percent Time BG in Range 70-140 mg/dL
Additional measure of glycemic variability, as reflected by CGM measures, % time in the range of 70-140 on CGM
Time frame: continuous over the 72 hour investigation period
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Study Period: Percent Time BG in Range 70-140 mg/dL | 70.6 % of time |
| Closed Loop Insulin | Study Period: Percent Time BG in Range 70-140 mg/dL | 89.2 % of time |
p-value: 0.074t-test, 2 sided