Islet Transplantation for Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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The complex program of insulin replacement for type 1 diabetes that is current clinical standard of care is difficult to implement for long periods of time, associated with an increased risk of severe hypoglycemia and implemented by less than 50 % of the population of such patients. Outcomes of transplantation of isolated human islets have substantially improved and been performed at about 40 institutions around the world. We are proposing a clinical phase 1/phase 2 study of islet transplantation alone evaluating safety and efficacy in five patients with type 1 diabetes. Islet isolation from deceased donor pancreases will be performed at the Mayo Rochester Islet Isolation facility and islets infused by Interventional Radiology into the portal venous system. Following islet infusion, patients will be hospitalized for 48 hours in the General Clinical Research Center (GCRC) or at the Rochester Methodist Hospital. Multiple safety and efficacy outcomes will be followed on multiple occasions during the first year and periodically thereafter.

Official Title
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Islet Transplantation for Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Biological: Islet Transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Duration of diabetes: 5 years or more Type 1 diabetes with C-peptide < 200 pmol/L and a simultaneous plasma glucose between 60 and 250 mg/dl Complex insulin program supervised by an endocrinologist for at least 6 months Hypoglycemic unawareness diagnosed using Clarke Awareness Questionnaire Body weight < 70 kg Body Mass Index < 30 kg/m^2 Insulin requirement < 40 units/day by multiple daily injections or < 30 units /day by external insulin pump or < 0.6 unit/kg/day with a HbA1c < 7.0 % ( Normal < 6 %) No overt cardiovascular disease No laser treatment for retinopathy Retinopathy diagnosed by ophthalmologist to be stable and requiring no further evaluation for at least one year Women of child bearing age will have a negative pregnancy test at screening and time of trial initiation Women enrolled in the trial should be willing to practice birth control while on immunosuppression No psychologic issues that would interfere with adherence to safe clinical practice Blood type (ABO) compatibility No evidence of chronic liver disease (aspartate aminotransferase (AST) < 2.5 times normal, alanine aminotransferase (ALT) < 2.5 times normal, international normalized ratio (INR) < 1.4, No evidence of fatty liver on abdominal ultrasound. Exclusion Criteria: Ongoing infection Ongoing alcohol or drug abuse Clinical portal hypertension Gall stones Liver hemangioma on ultrasound interfering with islet infusion Lack of updated immunization Unstable cardiovascular status as defined by: Myocardial infarction/acute coronary syndrome in last year Significant coronary atherosclerosis on angiography Active ischemia at evaluation Pre-trial low-density lipoprotein (LDL) cholesterol > 100 and triglycerides > 200 mg/dl with or without lipid lowering therapy Active peptic ulcer disease Previous organ transplantation except islet transplantation Negative serology for Epstein-Barr Virus (EBV) or ongoing acute EBV infection Previous malignancy unless 5 years ago basal cell cancer squamous cell cancer Requiring steroid therapy for any reason Positive Purified Protein Derivative (PPD - Tuberculosis Skin Test) Serological evidence of HIV, Hepatitis C or Hepatitis B Chronic anemia Single Antigen B (SAB) normalized value >1500 Renal disease Iothalamate clearance < 70 cc/min 24 hour urine protein > 500 mg/24 hours

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Islet Transplant<br>Subjects will receive standard intraportal transplantation or portal venous system infusion via laparotomy of purified pancreatic islets. | Biological: Islet Transplant<br>* Purified pancreatic islets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Number of Hypoglycemic Events After Transplant | Hypoglycemia is an abnormally diminished content of glucose in the blood. | 3, 6, 9, and 12 months since islet transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Glycated Hemoglobin (HbA1c) Since Transplant | HbA1c is a lab test that shows the average level of blood sugar (glucose) over the previous 3 months. It shows how well the subject is controlling his/her diabetes. | 3, 6, 9, and 12 months since islet transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypoglycemic unawareness