Efficacy of Islet After Kidney Transplantation

NCT00468117 | Completed Phase 3 DMC

• 1 other identifier: DAIT CIT-06
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 10

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 benefit of islet transplantation in type 1 diabetic (T1D) kidney transplant recipients.

Conditions

Type 1 Diabetes Mellitus

Keywords

Hypoglycemia; Kidney Transplant; Insulin independence; Islet Transplantation; Intensive Insulin Therapy

Outcome Measures

Primary Outcomes (1)

• Proportion of patients w/HbA1c </= to 6.5% and an absence of severe hypoglycemic events or a reduction in HbA1c of at least 1 point and an absence of severe hypoglycemic events

  At 1 year after first islet infusion

Secondary Outcomes (1)

• Reduction in insulin requirements, HbA1c, MAGE, LI, HYPO score, fasting glucose, beta score, serum creatinine, c-peptide levels, MMTT, Clarke Survey, FSIGT, CGMS, number of hypoglycemic events, renal impact, cardiovascular impact, and quality of life

  At 1 year after first islet infusion and/or 1 year after final islet infusion

Study Arms (1)

Islet transplantation

EXPERIMENTAL

Up to three separate islet transplants will occur and a regimen of immunosuppressive medications consisting of antithymocyte globulin (ATG) and etanercept throughout study.

Procedure: Islet transplantation; Biological: Antithymocyte Globulin; Biological: Daclizumab or Basiliximab; Biological: Etanercept; Biological: Allogenic human purified pancreatic islets

Interventions

Islet transplantation PROCEDURE

Islet transplantation

Antithymocyte Globulin BIOLOGICAL

Participants will begin receiving ATG 2 days prior to the initial islet transplant and will continue to receive ATG until Day 2 post-transplant.

Also known as: ATG

Islet transplantation

Daclizumab or Basiliximab BIOLOGICAL

Daclizumab or Basiliximab will be used for subsequent transplants.

Islet transplantation

Etanercept BIOLOGICAL

Etanercept will be given on the day of transplant and on Days 3, 7, and 10 post-transplant.

Islet transplantation

Allogenic human purified pancreatic islets BIOLOGICAL

200 ml suspension of allogenic human purified islets

Islet transplantation

Eligibility Criteria

• Age: 18 Years - 68 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 a sum of age and insulin dependent diabetes duration of at least 28;
• Absent stimulated C-peptide (defined as less than 0.3 ng/ml) 60 and 90 minutes post-mixed-meal tolerance test;
• Received kidney transplant for ESRD and are taking appropriate calcineurin inhibitor (CNI) based maintenance immunosuppressive therapy;
• Stable renal function as defined as creatinine of no more than one third greater than the average creatinine determination performed in the 3 previous months prior to islet transplantation, until rejection, obstruction or infection is ruled out;
• Intensive diabetes management followed by reduced awareness of hypoglycemia or an HbA1c ≥ 7.5%.

You may not qualify if:

• Body mass index (BMI) greater than 30 kg/m2 or weight more than 90 kg;
• Insulin requirement of \>1.0 IU/kg/day or \<15 U/day;
• Other (non-kidney) organ transplants except prior failed pancreatic graft where the graft failed within the first two weeks due to thrombosis, followed by pancreatectomy and the pancreas transplant occurred more than 6 months prior to enrollment;
• Untreated proliferative diabetic retinopathy;
• Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg;
• Calculated glomerular filtration rate of less than 40 ml/min/1.73meter-squared. More information about this criterion is in the protocol;
• Proteinuria (albumin/creatinine ratio or ACr \> 300 mg/g) of new onset since kidney transplantation;
• Either Class I or Class II panel-reactive anti-HLA antibodies \> 50%; Participants with either Class I or Class II panel reactive anti-HLA antibodies of 50% or less will be excluded if any of the following are detected:
• Positive cross match;
• Islet donor-directed anti-HLA antibodies detected my Luminex Single Antigen/specificity bead assay, including weakly reactive antibodies that would not be detected by a flow cross-match; or
• Antibodies to the renal donor (i.e. presumed de novo).
• Pregnant, breastfeeding, or unwilling to use effective contraception throughout the study and 4 months after study completion;
• Active infection, including hepatitis B, hepatitis C, HIV, or tuberculosis. More information about this criterion is in the protocol.
• Negative for Epstein-Barr virus (EBV) by (VCA) IgG determination;
• Invasive aspergillus infection, histoplasmosis, and coccidioidomycosis infection one year prior to study enrollment;

Sponsors & Collaborators

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

Study Sites (10)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

University of Miami

Miami, Florida, 33124, United States

Location

Emory Universtiy

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60208, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60607, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

University of Alberta

Edmonton, Alberta, T6G 2C8, Canada

Location

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID) website
• Clinical Islet Transplantation Consortium website

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia

Interventions

Islets of Langerhans Transplantation; Antilymphocyte Serum; Daclizumab; Basiliximab; 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)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Endocrine Surgical Procedures; Surgical Procedures, Operative; Transplantation; 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; 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

• James F. Markmann, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2007
• First Posted: May 2, 2007
• Study Start: January 1, 2007
• Primary Completion: July 1, 2015
• Study Completion: July 5, 2017
• Last Updated: October 20, 2017

Record last verified: 2017-10

Locations

US (9); CA (1)