Trial record 1 of 1 for:    cit06
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Efficacy of Islet After Kidney Transplantation

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00468117
First received: May 1, 2007
Last updated: May 30, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Type 1 Diabetes Mellitus
Procedure: Islet transplantation
Biological: Antithymocyte Globulin
Biological: Daclizumab or Basiliximab
Biological: Etanercept
Biological: Allogenic human purified pancreatic islets
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Islet Transplantation in Type 1 Diabetic Kidney Allograft Recipients: Efficacy of Islet After Kidney Transplantation (CIT-06)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • 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 [ Time Frame: At 1 year after first islet infusion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: At 1 year after first islet infusion and/or 1 year after final islet infusion ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: January 2007
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Islet transplantation
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
Participants will begin receiving ATG 2 days prior to the initial islet transplant and will continue to receive ATG until Day 2 post-transplant.
Other Name: ATG
Biological: Daclizumab or Basiliximab
Daclizumab or Basiliximab will be used for subsequent transplants.
Biological: Etanercept
Etanercept will be given on the day of transplant and on Days 3, 7, and 10 post-transplant.
Biological: Allogenic human purified pancreatic islets
200 ml suspension of allogenic human purified islets

Detailed Description:

Type 1 diabetes is commonly treated with the administration of insulin, either by multiple insulin injections or by a continuous supply of insulin through a wearable pump. Insulin therapy allows long-term survival in individuals with type 1 diabetes; however, it does not guarantee constant normal blood sugar control. Because of this, long-term type 1 diabetic survivors often develop vascular complications, such as diabetic retinopathy, an eye disease that can cause poor vision and blindness, and diabetic nephropathy, a kidney disease that can lead to kidney failure and thus kidney transplant. Some individuals with type 1 diabetes develop hypoglycemia unawareness, a life-threatening condition that is not easily treatable with medication and is characterized by reduced or absent warning signals for hypoglycemia. For such individuals, pancreas or pancreatic islet transplantation are possible treatment options. The purpose of this study is to assess the benefit of islet transplantation in type 1 diabetic kidney transplant recipients.

Participants in this study will be type I diabetics who have received a kidney transplant for ESRD.. If subjects have not received ITT in the 12 months prior to enrollment, they must undergo a period of standardized diabetes care by an experienced diabetologist at the transplant center using the current ADA's standards of medical care in diabetes. Throughout the study, all participants will remain on the immunosuppressive therapy intended for their kidney. Participants will receive up to three separate islet transplants and a regimen of immunosuppressive medications consisting of antithymocyte globulin (ATG) and etanercept. They will begin receiving ATG 2 days prior to transplant and will continue to receive ATG until Day 2 post-transplant. Etanercept will be given on the day of transplant and on Days 3, 7, and 10 post-transplant.

Transplantations will involve an inpatient hospital stay and infusion of islets into a branch of the portal vein. Participants who do not achieve or maintain insulin independence by Day 30 post-transplant will be considered for a second islet transplant. Participants who remain dependent on insulin for longer than 30 days after the second transplant and who show partial graft function will be considered for a third islet transplant. Daclizumab will be used in place of ATG for the second and third transplants, if they are necessary. Participants who do not meet the criteria for a subsequent transplant will enter a reduced follow-up period.

There will be approximately 15 study visits. A physical exam, review of adverse events, and blood collection will occur at most visits. A chest x-ray, abdominal ultrasound, electrocardiogram, quality of life questionnaires, and urine collection will occur at some visits. Participants will also test their own blood glucose levels throughout the study. A 36-month follow-up period will take place after the participant's last transplant, consisting of 8 additional visits.

  Eligibility

Ages Eligible for Study:   18 Years to 68 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 (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%

Exclusion Criteria:

  • 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/1.73m2. 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:

    1. Positive cross match
    2. 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
    3. 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 by IgG determination
  • Invasive aspergillus infection, histoplasmosis, and coccidioidomycosis infection 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
  • History of Factor V Leiden mutation
  • Any coagulopathy or medical condition requiring long-term anticoagulant therapy after transplantation or individuals with an INR greater than 1.5
  • Severe co-existing cardiac disease, characterized by any one of these conditions:

    1. Recent MI (within past 6 months);
    2. Evidence of ischemia on functional cardiac exam within the last year;
    3. Left ventricular ejection fraction < 30%; or
    4. Valvular disease requiring replacement with prosthetic valve.
  • Persistent elevation of liver function tests at the time of study entry. Persistent serum glutamic-oxaloacetic transaminase (SGOT [AST]), serum glutamate pyruvate transaminase (SGPT [ALT],) alkaline phosphatase or total bilirubin, with values > 1.5 times normal upper limits will exclude a subject.
  • Active infections (except mild skin and nail fungal infections).
  • Acute or chronic pancreatitis
  • Active peptic ulcer disease, symptomatic gallstones, or portal hypertension
  • Treatment with any anti-diabetic medication other than insulin within the past 4 weeks
  • Use of any investigational agents within the past 4 weeks
  • Received a live attenuated vaccine(s) within the past 2 months
  • Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial
  • Male participants with elevation of prostate specific antigen (PSA) of more than 4 unless cancer has been excluded
  • Any condition other than T1D as the primary cause of end stage renal disease (ESRD) in the native kidney
  • Positive screen for BK virus by polymerase chain reaction (PCR) determination at time of screening
  • A previous islet transplant
  • A kidney transplant recipient with T1D who has an HbA1c < 7.5% and no history of severe hypoglycemia
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00468117

Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Florida
University of Miami
Miami, Florida, United States
United States, Georgia
Emory Universtiy
Atlanta, Georgia, United States
United States, Illinois
Northwestern University
Chicago, Illinois, United States
University of Illinois at Chicago
Chicago, Illinois, United States, 60607
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada
Sponsors and Collaborators
Investigators
Principal Investigator: James F. Markmann, MD, PhD Massachusetts General Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00468117     History of Changes
Other Study ID Numbers: DAIT CIT-06
Study First Received: May 1, 2007
Last Updated: May 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Hypoglycemia
Kidney Transplant
Insulin independence
Islet Transplantation
Intensive Insulin Therapy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Antilymphocyte Serum
Daclizumab
TNFR-Fc fusion protein
Basiliximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gastrointestinal Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 21, 2014