Islet Transplantation in Type 1 Diabetic Patients Using the University of Illinois at Chicago (UIC) Protocol
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.
Type 1 Diabetes Mellitus
Drug: Islets of Langerhans transplantation
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Islet Transplantation in Type 1 Diabetic Patients Using the UIC Protocol, Phase 3|
- Safety: Incidence and severity of events related to islet infusion, immunosuppression, and islet preparations [ Time Frame: One year after first and last islet transplants ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: Yes ]
- Insulin independence [ Time Frame: One year after the last transplant ] [ Designated as safety issue: No ]
- Hypoglycemic episodes by HYPO score [ Time Frame: One year after the last transplant ] [ Designated as safety issue: No ]
- Glucose variability and hypoglycemia duration [ Time Frame: One year after the last transplant ] [ Designated as safety issue: No ]
|Study Start Date:||June 2007|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
All subjects will receive up to three 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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00679042
|Contact: Jose Oberholzer, MDfirstname.lastname@example.org|
|Contact: Wesley Schrock, BAemail@example.com|
|United States, Illinois|
|University of Illinois at Chicago Medical Center||Recruiting|
|Chicago, Illinois, United States, 60612|
|Principal Investigator: Jose Oberholzer, MD|
|Principal Investigator:||Jose Oberholzer, MD||University of Illinois at Chicago|