Diabetes
Conditions
Keywords
Diabetes, Insulin Resistance, Nitrite, Pancreatic islet cells, Autotransplantation, Ischemia reperfusion injury, Mitigation, Cure, Nitric oxide, Sodium nitrite, Islet cell, Survival, Pancreas, Liver
Brief summary
This study seeks to investigate the effects of administering nitrite to pancreatic islet cells that have been removed from a patient for autotransplantation.
Detailed description
Patients diagnosed with chronic pancreatitis or recurrent acute pancreatitis may acquire insulin-dependent diabetes due to islet cell destruction. Therefore, islet cell autotransplantation is the optimal therapeutic approach for many of these patients. Islet cell autotransplantation is typically done by excision of the pancreas, followed by isolation of the islet cells and then infusion of these cells into the sinusoids of the liver. Isolation of the islet cells occurs in an ischemic and hypoxic environment, resulting in ischemia reperfusion (IR) injury and destruction of islet cells following infusion into the sinusoids. Hence, strategies to prevent IR injury and subsequent islet cell destruction, such as the administration of inhaled nitric oxide (NO) or sodium nitrite (NaNO2) could enhance islet cell survival following reperfusion, also decreasing long-term insulin requirement. The purpose of this study is to determine if NO administered by infusion in patients undergoing islet cell auto transplantation, will inhibit islet cell destruction, increase diabetes cure rate (decrease the amount of and/or the need for long-term insulin requirement), decrease the ischemic injury (reduces the injury to the islet cells from a decrease in oxygen levels during procurement of the islet cells) during islet cell procurement, and decrease IR injury following islet cell infusion. The primary endpoints of the study are exogenous insulin use, HgbA1c levels post-operatively, and blood glucose levels.
Interventions
OTHERControl
A saline infusion will be administered during the pre-isolation and post-isolation phases.
DRUGPre-Isolation Infusion
A nitrite infusion will be administered during the pre-isolation phase and a saline infusion will be administered during the post-isolation phase.
DRUGPost-Isolation Infusion
A saline infusion will be administered during the pre-isolation phase and a nitrite infusion will be administered during the reperfusion phase.
Sponsors
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients greater than or equal to 18 years of age * Scheduled to undergo Islet Cell auto-transplantation by Dr. Jared White or Dr. Bart Rose * Subjects who can provide informed written consent and are willing to do so
Exclusion criteria
-Any patient with liver disease or unsuitable for surgery (as determined by the surgeon)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prior to Infusion Blood Glucose Serum Levels | Between the time of induction and the time immediately prior to infusion of either nitrite or saline | Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc. |
| Pre-islet Cell Infusion Blood Serum Glucose Levels | Five minutes prior to the infusion of islet cells | Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc. |
| 20 Minutes After Islet Cells Blood Serum Glucose Levels | 20 minutes after the infusion of Islet Cells | Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc. |
| 40 Minutes After Islet Cells Blood Serum Glucose Levels | 40 minutes after the infusion of Islet Cells | Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc. |
| 24 Hours Post Operative Blood Samples Serum Glucose Levels | 24 hours post operatively | Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc. |
| 48 Hours Post Operative Blood Samples Serum Glucose Levels | 48 hours post operatively | Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc. |
| 72 Hours Post Operative Blood Samples Serum Glucose Levels | 72 hours post operatively | Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc. |
| 96 Hours Post Operative Blood Samples Serum Glucose Levels | 96 hours post operatively | Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Group Control: A saline infusion will be administered during the pre-isolation and post-isolation phases. | 1 |
| Pre-Isolation Infusion Pre-Isolation Infusion: A nitrite infusion will be administered during the pre-isolation phase and a saline infusion will be administered during the post-isolation phase. | 1 |
| Post-Isolation Infusion Post-Isolation Infusion: A saline infusion will be administered during the pre-isolation phase and a nitrite infusion will be administered during the reperfusion phase. | 2 |
| Total | 4 |
Baseline characteristics
| Characteristic | Control Group | Pre-Isolation Infusion | Post-Isolation Infusion | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United States | 1 participants | 1 participants | 2 participants | 4 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 0 / 2 |
| other Total, other adverse events | 0 / 1 | 0 / 1 | 0 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 2 |
Outcome results
Primary
20 Minutes After Islet Cells Blood Serum Glucose Levels
Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time frame: 20 minutes after the infusion of Islet Cells
Population: The study did not reach sufficient enrollment power for statistical analysis.
Primary
24 Hours Post Operative Blood Samples Serum Glucose Levels
Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time frame: 24 hours post operatively
Population: The study did not reach sufficient enrollment power for statistical analysis.
Primary
40 Minutes After Islet Cells Blood Serum Glucose Levels
Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time frame: 40 minutes after the infusion of Islet Cells
Population: The study did not reach sufficient enrollment power for statistical analysis.
Primary
48 Hours Post Operative Blood Samples Serum Glucose Levels
Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time frame: 48 hours post operatively
Population: The study did not reach sufficient enrollment power for statistical analysis.
Primary
72 Hours Post Operative Blood Samples Serum Glucose Levels
Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time frame: 72 hours post operatively
Population: The study did not reach sufficient enrollment power for statistical analysis.
Primary
96 Hours Post Operative Blood Samples Serum Glucose Levels
Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time frame: 96 hours post operatively
Population: The study did not reach sufficient enrollment power for statistical analysis.
Primary
Pre-islet Cell Infusion Blood Serum Glucose Levels
Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time frame: Five minutes prior to the infusion of islet cells
Population: The study did not reach sufficient enrollment power for statistical analysis.
Primary
Prior to Infusion Blood Glucose Serum Levels
Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time frame: Between the time of induction and the time immediately prior to infusion of either nitrite or saline
Population: The study did not reach sufficient enrollment power for statistical analysis.