Allogenic Islet Cell Transplantation

Allogenic Islet Cells (Human, U. of Chicago) Administered Via Intraportal Infusion; and Immunosuppressive Therapy

The purpose of this study is to determine the safety of transplanting human islet cells for controlling hyperglycemia in brittle and/or complex patients with type 1 diabetes. In addition, initial observations will be made with regards to the effectiveness of reversing hypoglycemia with this treatment. The "Edmonton Protocol" of using specific anti-rejection drugs without steroids is also being evaluated.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Procedure: Intraportal infusion of islet cells; Drug: Allogenic islet cells (human, U. Chicago)

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 58 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have type I diabetes mellitus, documented by undetectable C-peptide. Patients must have been diabetic for at least five years, and be aged 18 - 58 years.
• Patients must be on an intensive regimen of glucose monitoring and exogenous insulin injection (defined as greater than or equal to three checks and injections per day). This regimen must be prescribed and supervised by the patient's diabetologist.

• Despite intensive therapy, patients must have at least one of the following:

  • Brittle diabetes (metabolic instability), as defined by elevated mean amplitude of glycemic excursion;
  • Hypoglycemic unawareness, with at least one episode in the past two years in which hypoglycemia required the assistance of another person (e.g., family member, emergency medical technician [EMT], etc.), and was associated with a fingerstick blood glucose (FSBG) of < 50 mg/dl and prompt recovery after administration of oral glucose, intravenous glucose, or glucagon;
  • Progressive complications of diabetes (nephropathy manifested by proteinuria, retinopathy documented by an ophthalmologist after dilated eye exam, or neuropathy as determined by a neurologist).
• Patients must be able to give informed consent.

Exclusion Criteria:

• Failure to meet inclusion criteria
• Panel of Reactive Antibody (PRA) > 10%
• Creatinine clearance < 80 mL/min
• Prior organ transplant
• Portal hypertension: this refers to portal hypertension diagnosed previously by any means, or, by the investigators' evaluation, symptoms and/or signs of liver dysfunction with or without portal hypertension including, but not limited to, jaundice, ascites, encephalopathy, spider angiomata, coagulopathy, or peri-umbilical venous engorgement. Elevated portal pressures, as measured during intended islet infusion, may also result in discontinuation of infusion.
• Abnormal liver function tests (> 2 times the upper limit of normal as defined by the University of Chicago Clinical Laboratory)
• History of malignancy. Any history of malignancy in a patient who has had an "adequate" period of no evidence of neoplastic disease should not rule out individuals from enrolling in this study. Rather, pre-enrollment screening for malignancy will follow current established guidelines as for solid-organ transplant. These current guidelines appear in Kasiske, B.L., et al. "The Evaluation of Renal Transplant Candidates: Clinical Practice Guidelines," American Journal of Transplantation 1 (Supplement 2): 12-22, 2001.
• Active peptic ulcer disease
• Pregnancy, or inability to comply with contraceptive regimen
• Severe unremitting gastroparesis or diarrhea
• Active infection
• Serologic positivity for HIV and/or hepatitis
• Chest radiographic abnormality consistent with neoplastic or infectious disease
• Major ongoing psychiatric illness and/or substance abuse
• Noncompliance with current medical regimen
• Obesity (body mass index [BMI] > 28)
• Any other medical condition precluding safe transplantation and immunosuppression
• Ejection fraction < 30%
• Myocardial infarction (MI) within the past 6 months
• Known allergies or hypersensitivity to immunosuppressive agents used in this protocol
• Inability to provide written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Transplant

Procedure: Intraportal infusion of islet cells; Intraportal infusion of islet cell through the portal vein in the liver.; Drug: Allogenic islet cells (human, U. Chicago); Human allogenic islet cells. Immunosuppression varies but may include prograf, celcept, sirolimus, prednisone. Dosage will vary per patient based on weight. Patients will receive immunosuppression medications while islet cells are functioning.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
decrease in insulin requirement - Subjects able to maintain fasting blood glucose concentrations below 126 mg/dL and 2-hour post prandial levels below 180 mg/dL will be considered to be insulin independent.	Monthly
decrease in incidence of hypoglycemic events	Monthly

Secondary Outcome Measures

Outcome Measure	Time Frame
absence of complications from the procedure and side effects of the medication	Monthly

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Piotr Witkowski, MD, Ph.D., University of Chicago

Publications and helpful links

General Publications

• Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000 Jul 27;343(4):230-8. doi: 10.1056/NEJM200007273430401.

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 8, 2005
• First Posted (Estimated): September 12, 2005

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Islet Cell Transplant; Human islet cell infusion; Juvenile-onset diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 12176A; BB-IND 11228