Islet Transplantation for Type 1 Diabetes
1 other identifier
interventional
36
5 countries
9
Brief Summary
The purpose of this study is to test whether the islet cell transplantation procedures and results from a previous study in Edmonton, Canada, can be repeated. The study also is designed to learn more about diabetes control using islet cell transplantation. This is a Phase I/II study (a study that examines effectiveness and looks for side effects). The transplanting of islet cells has been studied in Type 1 diabetic patients whose blood sugar levels will not stay normal, despite intensive insulin therapy. A recent study conducted in Edmonton, Canada, was able to demonstrate that islet transplantation led to insulin independence in a majority of the patients treated. This study extends the results obtained from the Edmonton study, which used islet transplantation in Type 1 diabetic patients with steroid-free immunosuppression.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Apr 2001
Longer than P75 for phase_2
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2001
CompletedFirst Submitted
Initial submission to the registry
April 13, 2001
CompletedFirst Posted
Study publicly available on registry
August 31, 2001
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2005
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2010
CompletedResults Posted
Study results publicly available
October 17, 2012
CompletedMarch 15, 2017
February 1, 2017
4.2 years
April 13, 2001
September 13, 2012
February 6, 2017
Conditions
Outcome Measures
Primary Outcomes (1)
Percent of Participants That Achieved Insulin Independence With Adequate Control of Blood Glucose Levels at One Year Post Final Islet Transplantation.
Insulin independence: exogenous insulin not required and glycemic control is achieved as defined by maintaining 1.) a blood glycosylated hemoglobin (HbA1c) level \< 6.5% (Normal:\<5.7%; pre-diabetes: 5.7% -6.4%; diabetes: 6.5% or higher),2) a blood glucose level after an overnight fast not exceeding 140 mg per deciliter (dL) more than three times in any week (Normal: 70 to 120 mg/dL), and 3)not exceeding a 2-hour postprandial blood glucose level of 180 mg/dL more than four times per week (Normal: \<140mg/dL if \<=50 years of age, \<150 mg/dL for ages 50-60 years and \<160 mg/dL for ages 60+)
One year status post participant receipt of final islet transplantation
Secondary Outcomes (3)
Percent of Participants With Partial Islet Function One Year Post Final Islet Transplantation.
One year post receipt of final islet transplantation
Percent of Participants That Achieved Insulin Independence From First Transplant
First transplantation until end of study (up to six years post final transplantation)
Percent of Participants With Detectable Fasting Basal C-Peptide Levels
Two years post first transplantation
Study Arms (1)
Islet Transplantation
EXPERIMENTALAll study participants
Interventions
Participants will receive portal vein islet infusions (up to 3), e.g., islet transplantations, with a targeted total of exceeding 10,000 islet equivalents per kilogram of body weight (IE/kg) per infusion. Up to three transplants are possible depending on individual results.
Administered at a dose of 0.2 mg/kg by mouth once pre-transplantation then 0.1 mg/kg daily post-transplantation. Dosing will be adjusted to achieve a trough peripheral blood level of 12-15 ng/mL x3 months after transplantation and 7-12 ng/mL for the remainder of the study.
Administered at a dose of 1 mg by mouth once pre-transplantation followed by 1 mg twice daily post transplantation. Levels will be adjusted to achieve a peripheral blood trough level of 3-6 ng/mL for maintenance immunosuppression.
Administered at a dose of 1 mg/kg intravenously immediately pre-transplantation and 2, 4, 6, and 8 weeks post-transplantation, totaling 5 doses(over 8 weeks). Further daclizumab dosing may be necessary based on individual results and islet transplantation needs.
Eligibility Criteria
You may qualify if:
- Patients may be eligible for this study if they:
- Have had Type 1 diabetes mellitus for more than 5 years, and are exhibiting 1 of the following, despite intensive insulin management efforts: a) hypoglycemic unawareness, as defined by inability to sense hypoglycemia until the blood glucose falls to less than 54 mg/dL; b) metabolic instability, with 2 or more episodes of severe hypoglycemia (defined as an event with symptoms consistent with hypoglycemia in which the patient requires the assistance of another person and which is associated with a blood glucose below 54 mg/dL) or 2 or more hospital visits for diabetic ketoacidosis over the last year; or c) despite efforts at optimal glucose control, progressive secondary complications of diabetes as defined by retinopathy, nephropathy, or neuropathy.
- Are 18 to 65 years of age.
You may not qualify if:
- Patients will not be eligible for this study if they:
- Have had severe cardiac disease as defined by: a) recent myocardial infarction within the past 6 months; b) angiographic evidence of non-correctable coronary artery disease; or c) evidence of ischemia on a functional cardiac exam.
- Actively abuse alcohol or substances, including cigarette smoking (must not have smoked within the last 6 months).
- Have psychiatric problems that prevent them from being a suitable candidate for transplantation (such as schizophrenia, bipolar disorder, or major depression that is not controlled or stable on current medication).
- Have a history of not following prescribed regimens.
- Have active infection including hepatitis C virus, hepatitis B virus, human immunodeficiency virus (HIV), or Tuberculosis (TB) (or under treatment for suspected TB).
- Have a history of malignancy, except squamous or basal skin cancer.
- Weigh more than 70 kilograms or have a Body Mass Index (BMI) greater than 26 kg/m\^2 at time of screening.
- Have a C-peptide value of 0.3 ng/ml or more following a 5.0 gram intravenous arginine infusion challenge.
- Are unable to provide informed consent.
- Have gallstones or hemangioma in liver.
- Have untreated proliferative retinopathy.
- Are breast-feeding or pregnant, or intend to try and become pregnant (females) or to father a child (males), or fail to follow birth control methods.
- Have had a previous transplant, or evidence of anti-human leukocyte antigen (HLA) antibody.
- Have an insulin requirement of more that 0.7 International Units (IU)/kilograms/day.
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
University of Miami
Miami, Florida, 33136, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Washington University
St Louis, Missouri, 63110, United States
Benaroya Research Institute at Virginia Mason Research Center
Seattle, Washington, 98101, United States
University of Alberta
Edmonton, Alberta, Canada
Justus-Leibig University
Giessen, 35385, Germany
University of Milan
Milan, Italy
University of Geneva
Geneva, Switzerland
Related Publications (4)
Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, Secchi A, Brendel MD, Berney T, Brennan DC, Cagliero E, Alejandro R, Ryan EA, DiMercurio B, Morel P, Polonsky KS, Reems JA, Bretzel RG, Bertuzzi F, Froud T, Kandaswamy R, Sutherland DE, Eisenbarth G, Segal M, Preiksaitis J, Korbutt GS, Barton FB, Viviano L, Seyfert-Margolis V, Bluestone J, Lakey JR. International trial of the Edmonton protocol for islet transplantation. N Engl J Med. 2006 Sep 28;355(13):1318-30. doi: 10.1056/NEJMoa061267.
PMID: 17005949RESULTBrennan DC, Shannon MB, Koch MJ, Polonsky KS, Desai N, Shapiro J. Portal vein thrombosis complicating islet transplantation in a recipient with the Factor V Leiden mutation. Transplantation. 2004 Jul 15;78(1):172-3. doi: 10.1097/01.tp.0000128332.71657.ea. No abstract available.
PMID: 15257060RESULTBenedini S, Ermetici F, Briganti S, Codella R, Terruzzi I, Maffi P, Caldara R, Secchi A, Nano R, Piemonti L, Alejandro R, Ricordi C, Luzi L. Insulin-mimetic effects of short-term rapamycin in type 1 diabetic patients prior to islet transplantation. Acta Diabetol. 2018 Jul;55(7):715-722. doi: 10.1007/s00592-018-1141-z. Epub 2018 Apr 13.
PMID: 29654388DERIVEDGala-Lopez B, Kin T, O'Gorman D, Pepper AR, Senior P, Humar A, Shapiro AM. Microbial contamination of clinical islet transplant preparations is associated with very low risk of infection. Diabetes Technol Ther. 2013 Apr;15(4):323-7. doi: 10.1089/dia.2012.0297. Epub 2013 Feb 25.
PMID: 23438305DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Associate Director, Clinical Research Program
- Organization
- DAIT/NIAID
Study Officials
- PRINCIPAL INVESTIGATOR
James Shapiro, MD, PhD
University of Alberta
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 13, 2001
First Posted
August 31, 2001
Study Start
April 1, 2001
Primary Completion
June 1, 2005
Study Completion
August 1, 2010
Last Updated
March 15, 2017
Results First Posted
October 17, 2012
Record last verified: 2017-02
Data Sharing
- IPD Sharing
- Will share
Data access is provided to the public in : 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) portal.