Islet Transplantation in Type 1 Diabetic Patients Using...

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

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

This study is ongoing, but not recruiting participants.
Sponsored by: University of Illinois
Information provided by: University of Illinois
ClinicalTrials.gov Identifier: NCT00566813
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 I
Phase II

MedlinePlus related topics: Diabetes Diabetes Type 1 Islet Cell Transplantation
Drug Information available for: Tacrolimus Exenatide Etanercept Sirolimus Tacrolimus anhydrous Tumor Necrosis Factors Dacliximab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title: Islet Transplantation in Type 1 Diabetic Patients Using the Edmonton Protocol of Steroid Free Immunosuppression

Further study details as provided by University of Illinois:

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 2008
Arms Assigned Interventions
Group 1: Active Comparator
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
Group 2: Active Comparator
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.

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:
1. Reduced awareness of hypoglycemia at plasma glucose levels < 54 mg/dL
2. Metabolic lability/instability characterized by two or more episodes of severe hypoglycemia or hospital visits for diabetic ketoacidosis over the last year
3.

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

Exclusion Criteria:

*

Co-existing cardiac disease:
1. Myocardial infarction within past six months
2. Angiographic evidence of non-correctable coronary artery disease
3. 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 &#8805; 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
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
Investigators
Principal Investigator: Jose Oberholzer, MD University of Illinois

More Information

Division of Transplantation, University of Illinois at Chicago This link exits the ClinicalTrials.gov site

Responsible Party: University of Illinois at Chicago ( Margaret Moser )
Study ID Numbers: IND11807-2004-0532
Study First Received: November 30, 2007
Last Updated: August 4, 2008
ClinicalTrials.gov Identifier: NCT00566813 [history]
Health Authority: United States: Food and Drug Administration

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

Study placed in the following topic categories:
Sirolimus
Metabolic Diseases
Autoimmune Diseases
Exenatide
Daclizumab
Diabetes Mellitus
Endocrine System Diseases
Tacrolimus
TNFR-Fc fusion protein
Necrosis
Diabetes Mellitus, Type 1
Endocrinopathy
Glucose Metabolism Disorders
Metabolic disorder

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Immunologic Factors
Immune System Diseases
Physiological Effects of Drugs
Gastrointestinal Agents
Immunosuppressive Agents
Pharmacologic Actions
Hypoglycemic Agents
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents