Islet Transplantation in Type 1 Diabetic Patients Using the Edmonton Protocol of Steroid Free Immunosuppression

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2007 by University of Illinois at Chicago.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
University of Illinois at Chicago
ClinicalTrials.gov Identifier:
NCT00566813
First received: November 30, 2007
Last updated: August 5, 2011
Last verified: October 2007
  Purpose

The primary purpose of this study is to demonstrate the safety of allogeneic islet transplantation in type 1 diabetic patients performed at the University of Illinois at Chicago (UIC). The purpose is to reproduce the Edmonton protocol to demonstrate that pancreatic islets isolated at UIC are safe and of sufficient quality to provide reproducible graft function.


Condition Intervention Phase
Diabetes Mellitus, Type 1
Drug: Edmonton Protocol of steroid free immunosuppression
Drug: Islets of Langerhans Transplantation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Islet Transplantation in Type 1 Diabetic Patients Using the Edmonton Protocol of Steroid Free Immunosuppression

Resource links provided by NLM:


Further study details as provided by University of Illinois at Chicago:

Primary Outcome Measures:
  • Safety: adverse events, glucose control, hypoglycemic coma, renal function, liver function, lipids, PRA, hepatic blood flow, infections, immunosuppressive drug levels [ Time Frame: 1 year after the last transplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy: insulin independence, daily fasting blood glucose, HbA1c, oral glucose tolerance, mixed meal test, C-peptide, I.V. glucose tolerance, [ Time Frame: 1 year after the last transplant ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: November 2004
Estimated Study Completion Date: December 2013
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1
Islet transplantation and the Edmonton protocol of steroid free immunosuppression
Drug: Edmonton Protocol of steroid free immunosuppression
Islet of Langerhans 1-3 transplantations, daclizumab, sirolimus, tacrolimus
Other Name: Group 1 Edmonton Protocol
Active Comparator: Group 2
Edmonton Protocol,etanercept,exenatide
Drug: Islets of Langerhans Transplantation
Islets of Langerhans 1-3 transplantations, Edmonton protocol of steroid free immunosuppression (daclizumab 5 doses, sirolimus daily,tacrolimus BID, with additional etanercept 3 doses, and exenatide BID-TID for 6 months after each transplant.
Other Name: Group 2 Edmonton Protocol, etanercept, exenatide

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 1 diabetes > 5 years complicated by at least one of the following situations despite intensive insulin management:

    • Reduced awareness of hypoglycemia at plasma glucose levels < 54 mg/dL
    • Metabolic lability/instability characterized by two or more episodes of severe hypoglycemia or hospital visits for diabetic ketoacidosis over the last year
    • Progressive secondary complications of diabetes:

      • Retinopathy—three step progression using the ETDRS grading system or equivalent progression;
      • Nephropathy— microalbuminuria rise of 50 µg/min (72 mg/24h) over three months within the past two years despite using an ACE inhibitor;
      • Neuropathy—persistent gastroparesis, postural hypotension, neuropathic bowel or bladder, or severe peripheral neuropathy unresponsive to management

Exclusion Criteria:

  • Co-existing cardiac disease:

    • Myocardial infarction within past six months
    • Angiographic evidence of non-correctable coronary artery disease
    • Ischemia on functional cardiac exam d. Heart failure > NYHA II
  • Active alcohol or substance abuse or cigarette smoking
  • Psychiatric disorder: schizophrenia, bipolar disorder, or major depression that is unstable on medication
  • Non-adherence to prescribed regimens
  • Active infection including hepatitis C, hepatitis B, HIV
  • TB by history, current infection, or under treatment for suspected TB
  • History of malignancies except squamous or basal skin cancer
  • Stroke within the past 6 months
  • BMI > 26 kg/m2 or body weight > 70 kg at screening visit
  • C-peptide response to glucagon stimulation, any C-peptide ≥ 0.3 ng/mL
  • Inability to provide informed consent
  • Age less than 18 or greater than 65 years
  • Creatinine clearance < 85 mL/min/1.73 m2 by 24-hour urine collection
  • Serum creatinine > 1.5 mg/dL
  • Macroalbuminuria > 300 mg/24h
  • Baseline Hb < 12 gm/dL in women, < 13 gm/dL in men
  • Baseline liver function tests outside normal range
  • Untreated proliferative retinopathy
  • Positive pregnancy test, intent for pregnancy, male's intent to procreate, unwilling to use effective contraception, breast-feeding
  • Previous transplant or PRA reactivity > 20%)
  • Insulin requirement > 0.7 IU/kg/day
  • HbA1C > 12%
  • Hyperlipidemia
  • Chronic use of steroids
  • Use of coumadin or other anticoagulant (except aspirin) or PT INR > 1.5
  • Addison's disease
  • Allergy to radiographic contrast material
  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: NCT00566813

Locations
United States, Illinois
University of Illinois at Chicago
Chicago, Illinois, United States, 60612
Sponsors and Collaborators
University of Illinois at Chicago
Investigators
Principal Investigator: Jose Oberholzer, MD University of Illinois at Chicago
  More Information

Publications:
Responsible Party: Margaret Moser, University of Illinois at Chicago
ClinicalTrials.gov Identifier: NCT00566813     History of Changes
Other Study ID Numbers: IND11807-2004-0532
Study First Received: November 30, 2007
Last Updated: August 5, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Illinois at Chicago:
Diabetes Mellitus, Type 1
Islets of Langerhans Transplantation
Exenatide
Soluble tumor necrosis factor receptor

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Exenatide
TNFR-Fc fusion protein
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
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
Immunologic Factors
Immunosuppressive Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014