Nitrite Infusion in Islet Cell Transplantation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Nitrite Infusion in Islet Cell Transplantation: Test of Clinical Efficacy and Determination of Cytoprotective Mechanisms

Conditions
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Diabetes

Intervention / Treatment
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* Other: Control
* Drug: Pre-Isolation Infusion
* Drug: Post-Isolation Infusion


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br> | Other: Control<br>* A saline infusion will be administered during the pre-isolation and post-isolation phases.<br>|
| Experimental: Pre-Isolation Infusion<br> | Drug: Pre-Isolation Infusion<br>* A nitrite infusion will be administered during the pre-isolation phase and a saline infusion will be administered during the post-isolation phase.<br>|
| Experimental: Post-Isolation Infusion<br> | Drug: Post-Isolation Infusion<br>* A saline infusion will be administered during the pre-isolation phase and a nitrite infusion will be administered during the reperfusion phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Between the time of induction and the time immediately prior to infusion of either nitrite or saline | 
| 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. | Five minutes prior to the infusion of islet cells | 
| 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. | 20 minutes after the infusion of Islet Cells | 
| 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. | 40 minutes after the infusion of Islet Cells | 
| 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. | 24 hours post operatively | 
| 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. | 48 hours post operatively | 
| 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. | 72 hours post operatively | 
| 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. | 96 hours post operatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Insulin Resistance, Nitrite, Pancreatic islet cells, Autotransplantation, Ischemia reperfusion injury, Mitigation, Cure, Nitric oxide, Sodium nitrite, Islet cell, Survival, Pancreas, Liver