Peritransplant Deoxyspergualin in Islet Transplantation in Type 1 Diabetes

NCT00434850 | Completed Phase 2 DMC

• 1 other identifier: DAIT CIT-03
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

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 assess the safety and efficacy of deoxyspergualin (DSG), an immunosuppressant drug, on post-transplant islet function in people with type 1 diabetes who have not responded to intensive insulin therapy.

Conditions

Diabetes Mellitus, Type 1

Keywords

Insulin dependence; Hypoglycemia; Hyperglycemia unawareness

Outcome Measures

Primary Outcomes (1)

• Proportion of Insulin-independent Subjects

  75 days following the first islet transplant

Secondary Outcomes (30)

• Percent Reduction in Insulin Requirements

  75 days following the first and subsequent islet transplant

• Hemoglobin A1c (HbA1c)

  75 days following the first and subsequent islet transplant

• Mean Amplitude of Glycemic Excursions (MAGE)

  75 days following the first and subsequent islet transplant

• Glycemic Lability Index (LI)

  75 days following the first and subsequent islet transplant

• Ryan Hypoglycemia Severity Score (HYPO)

  75 days following the first and subsequent islet transplant

Study Arms (1)

Allogeneic Pancreatic Islet Cells

EXPERIMENTAL

Participants in this study can receive up to three separate islet transplants. They will begin receiving antithymocyte globulin (ATG) and sirolimus 2 days prior to the first islet transplant. ATG will continue to be given until Day 2 post-transplant. Participants will continue taking sirolimus for the duration of the study. On the day of transplant, participants will receive DSG and etanercept, in addition to ATG and sirolimus. The DSG infusion will be administered over 3 hours and will immediately precede the islet transplant. Participants will continue receiving daily 3-hour infusions of DSG through Day 6 post-transplant. Etanercept will also be administered on Days 3, 7, and 10 post-transplant. Tacrolimus will be administered on Day 1 post-transplant and continued throughout the study.

Biological: Allogeneic Pancreatic Islet Cells; Drug: Deoxyspergualin; Biological: Antithymocyte globulin; Biological: Daclizumab or basiliximab; Drug: Sirolimus; Drug: Tacrolimus; Biological: Etanercept

Interventions

Allogeneic Pancreatic Islet Cells BIOLOGICAL

Preparation of allogeneic pancreatic islet cells injected into the portal vein of the liver

Allogeneic Pancreatic Islet Cells

Deoxyspergualin DRUG

An anti-inflammatory agent that blocks proinflammatory cytokine production and inhibits T-cells and B-cells and affects antigen presenting cells.

Allogeneic Pancreatic Islet Cells

Antithymocyte globulin BIOLOGICAL

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

Allogeneic Pancreatic Islet Cells

Daclizumab or basiliximab BIOLOGICAL

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

Allogeneic Pancreatic Islet Cells

Sirolimus DRUG

Maintenance immunosuppressive therapy

Allogeneic Pancreatic Islet Cells

Tacrolimus DRUG

Maintenance immunosuppressive therapy

Allogeneic Pancreatic Islet Cells

Etanercept BIOLOGICAL

Blocks TNF-alpha which is toxic to islet cells

Allogeneic Pancreatic Islet Cells

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 of disease at less than 40 years of age; insulin dependence for at least 5 years at study entry; AND 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 clinical evaluations during the past 12 months prior to study enrollment
• At least one episode of severe hypoglycemia, defined as an event with one of the following symptoms: memory loss; confusion; uncontrollable behavior; irrational behavior; unusual difficulty in awakening; suspected seizure; seizure; loss of consciousness; or visual symptoms, in which the participant was unable to treat him/herself and which was associated with either a blood glucose level less than 54 mg/dl or prompt recovery after an oral carbohydrate, intravenous glucose, or glucagon administration in the 12 months prior to study enrollment.
• Reduced awareness of hypoglycemia. More information about this criterion, including the specific definition of hypoglycemia unawareness, is in the protocol.

You may not qualify if:

• Body mass index (BMI) greater than 30 kg/m2 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
• 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 using iohexol of less than 80 ml/min/1.73m2. More information about this criterion is in the protocol.
• Presence or history of macroalbuminuria (greater than 300 mg/g creatinine)
• Presence or history of panel-reactive anti-HLA antibody levels greater than 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 for 4 months after study completion
• Active infection, including hepatitis B virus, hepatitis C virus, HIV, or tuberculosis. More information about this criterion is in the protocol.
• Negative for Epstein-Barr virus by IgG determination
• Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection in the past year
• History of malignancy except for completely resected squamous or basal cell carcinoma of the skin
• Known active alcohol or substance abuse
• Baseline 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 (3)

University of Californinia, San Francisco

San Francisco, California, 94143, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Links

• Click here for the Clinical Islet Transplantation Consortium Web site

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia

Interventions

gusperimus; Antilymphocyte Serum; Daclizumab; Basiliximab; Sirolimus; Tacrolimus; Etanercept

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; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Immunoglobulin Constant Regions; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Study Officials

• Bernhard Hering, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

• Xunrong Luo, MD, PhD

  Northwestern University

  PRINCIPAL INVESTIGATOR

• Andrew Posselt, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

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: February 9, 2007
• First Posted: February 13, 2007
• Study Start: October 1, 2006
• Primary Completion: September 1, 2011
• Study Completion: November 1, 2013
• Last Updated: March 16, 2016

Record last verified: 2016-02

Locations

US (3)