Strategies to Improve Islet Survival

NCT00464555 | Completed Phase 2 DMC

• 1 other identifier: DAIT CIT-02
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation, combined with immunosuppressive medications and medications to support islet survival, for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.

Conditions

Type 1 Diabetes Mellitus

Keywords

Allogeneic Islets; Allogeneic Islet Transplantation; Type 1 diabetes mellitus; Type 1 diabetes; T1D; T1DM; Insulin dependence; Hypoglycemia unawareness in T1D; Islet transplant; Islet transplantation; Islet graft

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with insulin independence

  75 days after first transplant infusion

Secondary Outcomes (2)

• Reduction in insulin requirements, HbA1c, mean amplitude of glycemic excursions (MAGE), glycemic lability index (LI), Ryan hypoglycemia severity (HYPO) score, fasting glucose, glucose variation, beta score

  75 days and 1 year following the first and final infusion

• Quality of life measures

  75 days and 1 year following the first and final infusion, and 2 years after the final infusion

Study Arms (1)

Islet Transfusion and LSF

EXPERIMENTAL

Participants assigned to this group will receive an islet transfusion and an immunosuppressive medication regimen containing LSF.

Procedure: Islet transplant; Drug: Antithymocyte globulin; Drug: Basiliximab; Drug: Lisofylline; Drug: Sirolimus; Drug: Tacrolimus

Interventions

Islet transplant PROCEDURE

Transplantation of pancreatic islet cells

Islet Transfusion and LSF

Antithymocyte globulin DRUG

Immunosuppressive that selectively depletes activated T-cells and depletes resting T-cells in a dose-dependent manner.

Islet Transfusion and LSF

Basiliximab DRUG

Will replace antithymocyte globulin in all islet transplantations after the first one

Islet Transfusion and LSF

Lisofylline DRUG

An anti-inflammatory that may reduce the rate at which islet cells die.

Islet Transfusion and LSF

Sirolimus DRUG

Maintenance immunosuppressive therapy

Islet Transfusion and LSF

Tacrolimus DRUG

Maintenance immunosuppressive therapy

Islet Transfusion and LSF

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Mentally stable and able to comply with study procedures
• Clinical history compatible with type 1 diabetes with onset at less than 40 years of age, insulin dependence for at least 5 years at study entry, and a sum of age and insulin dependent diabetes duration of at least 28
• Absent stimulated C-peptide (less than 0.3 ng/mL) 60 and 90 minutes post-mixed-meal tolerance test
• Involvement of intensive diabetes management, defined as:
• Self-monitoring of glucose values no less than a mean of three times each day averaged over each week
• Administration of three or more insulin injections each day or insulin pump therapy
• Under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least three evaluations during the 12 months prior to study enrollment
• At least one episode of severe hypoglycemia in the past 12 months prior to study enrollment
• Reduced awareness of hypoglycemia. More information about this criterion, including specific definition of hypoglycemia unawareness, is in the protocol.

You may not qualify if:

• Body mass index (BMI) greater than 30 kg/m\^2 or weight less than or equal to 50 kg
• Insulin requirement of more than 1.0 IU/kg/day or less than 15 U/day
• Hemoglobin A1C (HbA1c) greater than 10%
• Untreated proliferative diabetic retinopathy
• Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg
• Measured glomerular filtration rate (GFR) using iohexol of less than 80 mL/min/1.73m2. More information about this criterion is in the protocol.
• Presence/history of macroalbuminuria (greater than 300 mg/g creatinine)
• Presence/history of panel-reactive anti-HLA antibodies above background by flow cytometry. More information about this criterion is in the protocol.
• Pregnant, breastfeeding, or unwilling to use effective contraception throughout the study and 4 months after study completion
• Presence of history of active infection, including hepatitis B, hepatitis C, human immunodeficiency virus (HIV), or tuberculosis (TB). More information about this criterion is in the protocol.
• Negative for Epstein-Barr virus (EBV) by IgG determination
• Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection within one year prior to study enrollment
• History of malignancy except for completely resected squamous or basal cell carcinoma of the skin
• Known active alcohol or substance abuse
• Baseline hemoglobin (Hgb) below the lower limits of normal, lymphopenia, neutropenia, or thrombocytopenia

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

University of Miami

Miami, Florida, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60607, United States

Location

Related Links

• Division of Allergy, Immunology, and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID)
• Click here for the Clinical Islet Transplantation Consortium Web site

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Antilymphocyte Serum; Basiliximab; lisofylline; Sirolimus; Tacrolimus

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Macrolides; Lactones; Organic Chemicals

Study Officials

• Camillo Ricordi, MD

  Department of Surgery, University of Miami Miller School of Medicine - Diabetes Research Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2007
• First Posted: April 23, 2007
• Study Start: December 1, 2006
• Primary Completion: November 1, 2011
• Study Completion: February 1, 2014
• Last Updated: April 26, 2016

Record last verified: 2016-03

Locations

US (2)