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Islet Transplantation in Type 1 Diabetic Patients Using the University of Illinois at Chicago (UIC) Protocol

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Jose Oberholzer, University of Illinois at Chicago
Sponsor:
Information provided by (Responsible Party):
Jose Oberholzer, University of Illinois at Chicago
ClinicalTrials.gov Identifier:
NCT00679042
First received: May 13, 2008
Last updated: May 24, 2017
Last verified: May 2017
  Purpose
In an earlier Phase 1/2 clinical trial using the Edmonton Protocol of steroid free immunosuppression, investigators at University of Illinois at Chicago (UIC) demonstrated the safety of islet preparation, iset transplantation, and medical treatment at UIC. Therefore, the primary purpose of the present Phase 3 clinical trial is to demonstrate the safety and efficacy of allogeneic islet transplantation in improving glycemic control in Type 1 diabetic patients using the UIC protocol that was developed and proven effective during the Phase 1/2 clinical trial.

Condition Intervention Phase
Type 1 Diabetes Mellitus Drug: Islets of Langerhans transplantation Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Islet Transplantation in Type 1 Diabetic Patients Using the UIC Protocol, Phase 3

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Safety: Incidence and severity of events related to islet infusion, immunosuppression, and islet preparations [ Time Frame: One year after first and last islet transplants ]
  • The proportion of subjects with an HbA1c ≤ 6.5% and free of severe hypoglycemic events [ Time Frame: One year after first and last islet transplants ]

Secondary Outcome Measures:
  • Insulin independence [ Time Frame: One year after the last transplant ]
  • Hypoglycemic episodes by HYPO score [ Time Frame: One year after the last transplant ]
  • Glucose variability and hypoglycemia duration [ Time Frame: One year after the last transplant ]

Estimated Enrollment: 1000
Study Start Date: June 2007
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
All subjects will receive up to 3 transplantations of allogeneic human islets of Langerhans.
Drug: Islets of Langerhans transplantation

Each subject may receive 1-3 transplantations of allogeneic human islets of Langerhans and the following medications:

Basiliximab 20 mg iv 2 hours before transplant and 20 mg iv 2 weeks post-transplant; Tacrolimus 1 mg p.o. bid adjusted to reach target trough levels of 3-6 ng/ml; Sirolimus 0.2 mg/kg loading dose, then 0.1 mg/kg p.o. daily adjusted to reach target trough levels of 10-15 ng/ml during the first 3 months post transplant and 7-10 ng/ml thereafter; Etanercept 50 mg iv 1 hour before transplant and 25 mg s.c. on days 3, 7,and 10 post-transplant; Exenatide 5-mcg s.c. bid for 1 week, then 10 mcg bid for 6 months after each transplant

Other Names:
  • Islets of Langerhan (Islets)
  • Basiliximab (Simulect®)
  • Tacrolimus (Prograf®)
  • Sirolimus (Rapamune®)
  • Etanercept(Enbrel®)
  • Exenatide (Byetta®)

Detailed Description:

This study is a Phase 3 single center, uncontrolled trial in which 1-3 allogeneic pancreatic islet transplants are performed for each study subject. Follow-up evaluations after transplant continue for 52 weeks after the final islet transplantation. Thereafter, subjects may enroll for a 5-year follow-up study and an additional 5 year to 10 year follow-up study to evaluate the function of the islets and to measure and regulate immunosuppressive drug levels and side effects.

The safety of islet transplantation depends primarily on the incidence of serious and unexpected complications or adverse events and the ability of the cell isolation laboratory to produce uncontaminated islet cell preparations with minimal endotoxin content.

All study subjects are followed for safety for one year. An independent Data Monitoring Committee (DMC), composed of 3 members who have training in medicine and/or organ transplantation, will review eligibility and safety data within 2 weeks after each islet transplantation and every two months thereafter. An independent monitor, who is knowledgeable about Good Clinical Practice (GCP) guidelines and regulations, monitors the study for compliance with 21 CFR and according to ICH GCP Guidelines. Within the Clinical Research Center, representatives of the Scientific Advisory Committee and the Research Subject Advocacy Program monitor safety. These entities report to the UIC Institutional Review Board (IRB), which also reviews safety data annually and on occurrence of serious adverse events. The principal investigator also reports serious adverse events to the US Food and Drug Administration (FDA).

Success: Islet transplantation is considered a success when subjects do not use insulin, and they achieve a fasting glucose level not exceeding 140 mg/dL more than three times in a week, and not exceeding two-hour post-prandial values of 180 mg/dL more than four times in a week.

Partial Success: Subjects who have a reduction in insulin requirements but who do not achieve insulin independence and present with a reduction in HbA1c and number of hypoglycemic episodes are considered to have partial success of islet transplantation. Reduction in insulin-requirements are assessed by comparing the pre-transplant insulin requirement recorded over two consecutive days (expressed as insulin units per kg) with the requirement on the two consecutive days preceding the subsequent islet infusion, and the requirements on two consecutive days at six months and again on two consecutive days at one year after the final transplant.

Failure: Absence of measurable levels of C-peptide after transplantation is considered as failure of islet cell transplantation.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 1 diabetes mellitus for more than 5 years complicated by the following situations that persist despite intensive insulin management efforts:
  • At least one episode of severe hypoglycemia in the past 3 years defined as an event with symptoms compatible with hypoglycemia in which the subject required the assistance of another person, and which was associated with either a blood glucose level <50 mg/dL (2.8 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration
  • Reduced awareness of hypoglycemia, defined by the absence of adequate autonomic symptoms at capillary glucose levels of <54 mg/dL (3 mmol/l) as reported by the subject

Exclusion Criteria:

  • Co-existing cardiac disease: myocardial infarction within the past 6 months, angiographic evidence of non-correctable coronary artery disease, ischemia on functional cardiac exam, heart failure
  • Active alcohol or substance abuse, including cigarette smoking (must be abstinent for six months)
  • Psychiatric disorder: schizophrenia, bipolar disorder, or major depression that is unstable on medication
  • History of 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
  • Family history of MEN2 or MCT
  • Stroke within the past 6 months
  • BMI >27 kg/m2
  • 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 75 years
  • Creatinine clearance <80 mL/min/1.73 m2 by 24-hour urine collection
  • Serum creatinine consistently >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 >80%
  • Insulin requirement >0.7 IU/kg/day
  • HbA1c >12%
  • Hyperlipidemia (fasting cholesterol >130 mg/dL or fasting triglycerides >200 mg/dL
  • Medical condition requiring chronic use of steroids
  • Use of Coumadin or other antiplatelet or anticoagulant therapy, or PT-INR >1.5
  • Factor V deficiency
  • Smoking tobacco
  • Addison's disease
  • Allergy to radiographic contrast material
  • Symptomatic cholecystolithiasis
  • Acute or chronic pancreatitis
  • Symptomatic peptic ulcer disease
  • Severe unremitting diarrhea, vomiting, or other gastrointestinal disorders that could interfere with medication absorption
  • Treatment with antidiabetic medication other than insulin within 4 weeks of enrollment
  • Use of any study medication within 4 weeks of enrollment
  • Received live attenuated vaccine(s) within 2 months of enrollment
  • Any medical condition that, in the opinion of the investigator, might interfere with safe participation
  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: NCT00679042

Contacts
Contact: Jose Oberholzer, MD 312-996-6771 jober@uic.edu
Contact: Andrea Molino, BS, BA 312-996-0530 amolino@uic.edu

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

Additional Information:
Responsible Party: Jose Oberholzer, Professor / Chief, Division of Transplantation, University of Illinois at Chicago
ClinicalTrials.gov Identifier: NCT00679042     History of Changes
Other Study ID Numbers: IND11807-2007-0330
Study First Received: May 13, 2008
Last Updated: May 24, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Jose Oberholzer, University of Illinois at Chicago:
Diabetes Mellitus Type 1
Type 1 Diabetes Mellitus
Islets of Langerhans Transplantation
Allogeneic Islet transplantation

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Tacrolimus
Sirolimus
Etanercept
Basiliximab
Exenatide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on June 23, 2017