Islet Transplantation in Type 1 Diabetes
1 other identifier
interventional
48
2 countries
8
Brief Summary
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation, combined with immunosuppressive medications, for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Oct 2006
Longer than P75 for phase_3
8 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
October 1, 2006
CompletedFirst Submitted
Initial submission to the registry
February 9, 2007
CompletedFirst Posted
Study publicly available on registry
February 13, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2014
CompletedJuly 17, 2019
July 1, 2019
5.9 years
February 9, 2007
July 11, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Proportion of participants with a HbA1c less than 7.0% AND free of severe hypoglycemic events
The proportion of participants with HbA1c ≤7.0% AND free of severe hypoglycemic events from Day 28 to Day 365 inclusive, following the first islet transplant, with the day of transplant designated Day 0.
From Day 28 to Day 365 (inclusive) following the first islet transplant, with the day of transplant designated Day 0
Secondary Outcomes (31)
Percent reduction in insulin requirements
75 days following the first and subsequent islet transplant
HbA1c on Day 75 Status Post the First and Subsequent Islet Transplant
75 days following the first and subsequent islet transplant
Mean amplitude of glycemic excursions (MAGE)
75 days following the first and subsequent islet transplant
Glycemic liability index (LI)
75 days following the first and subsequent islet transplant
Ryan hypoglycemia severity score (HYPO)
75 days following the first and subsequent islet transplant
- +26 more secondary outcomes
Study Arms (1)
Islet Transplantation
EXPERIMENTALParticipants will receive up to three separate islet transplants and a regimen of immunosuppressive medications consisting of antithymocyte globulin (ATG), sirolimus, and low-dose tacrolimus.
Interventions
200 ml suspension of allogenic human purified islets
Participants will begin receiving ATG 2 days prior to the first islet transplant. ATG will continue to be given until Day 2 post-transplant.
Participants will begin receiving sirolimus 2 days prior to the first islet transplant and will be given for the duration of the study.
On Day 1 post-transplant, participants will receive tacrolimus, which will also be taken for the duration of the study.
Etanercept will be taken on the day of transplant and Days 3, 7, and 10 post-transplant.
Basiliximab will be used in place of ATG for the second and third transplants, if they are necessary.
Eligibility Criteria
You may qualify if:
- Mentally stable and able to comply with study procedures
- Clinical history compatible with type 1 diabetes with onset of disease at less than 40 years of age, insulin dependence for at least 5 years at study entry, and a sum of age and insulin dependent diabetes duration of at least 28
- Absent stimulated C-peptide (less than 0.3 ng/ml) 60 and 90 minutes post-mixed-meal tolerance test
- Involvement of intensive diabetes management, defined as:
- Self-monitoring of glucose values no less than a mean of three times each day averaged over each week
- Administration of three or more insulin injections each day or insulin pump therapy
- Under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least three clinical evaluations during the past 12 months prior to study enrollment
- At least one episode of severe hypoglycemia in the past 12 months, defined as an event with one of the following symptoms: memory loss; confusion; uncontrollable behavior; irrational behavior; unusual difficulty in awakening; suspected seizure; seizure; loss of consciousness; or visual symptoms, compatible with hypoglycemia in which the individual required assistance of another subject was unable to treat him/herself person and which was associated with either a blood glucose level less than 54 mg/dl or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration in the 12 months prior to study enrollment
- Reduced awareness of hypoglycemia. More information about this criterion, including specific definition of hypoglycemia unawareness, is in the protocol.
You may not qualify if:
- Body mass index (BMI) greater than 30 kg/m2 or weight less than or equal to 50 kg
- Insulin requirement of more than 1.0 IU/kg/day or less than 15 U/day
- HbA1c greater than 10%
- Untreated proliferative diabetic retinopathy
- Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg
- Measured glomerular filtration rate using iohexol of less than 80 ml/min/1.73mm2. More information about this criterion is in the protocol.
- Presence or history of macroalbuminuria (greater than 300 mg/g creatinine)
- Presence or history of panel-reactive anti-HLA antibody levels greater than background by flow cytometry. More information about this criterion is in the protocol.
- Pregnant, breastfeeding, or unwilling to use effective contraception throughout the study and 4 months after study completion
- Presence or history of active infection, including hepatitis B, hepatitis C, HIV, or tuberculosis.
- Negative for Epstein-Barr virus by IgG determination
- Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection in the past year
- History of malignancy except for completely resected squamous or basal cell carcinoma of the skin
- Known active alcohol or substance abuse
- Baseline Hgb below the lower limits of normal, lymphopenia, neutropenia, or thrombocytopenia
- +20 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (8)
University of Callifornia, San Francisco
San Francisco, California, 94143, United States
University of Miami
Miami, Florida, 33136, United States
Emory University
Atlanta, Georgia, 30322, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Illinois, Chicago
Chicago, Illinois, 60612, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Alberta
Edmonton, Alberta, T6G028, Canada
Related Publications (8)
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: 17005949BACKGROUNDHarlan DM. Islet Transplantation for Hypoglycemia Unawareness/Severe Hypoglycemia: Caveat Emptor. Diabetes Care. 2016 Jul;39(7):1072-4. doi: 10.2337/dci16-0008. No abstract available.
PMID: 27330121BACKGROUNDRickels MR, Liu C, Shlansky-Goldberg RD, Soleimanpour SA, Vivek K, Kamoun M, Min Z, Markmann E, Palangian M, Dalton-Bakes C, Fuller C, Chiou AJ, Barker CF, Luning Prak ET, Naji A. Improvement in beta-cell secretory capacity after human islet transplantation according to the CIT07 protocol. Diabetes. 2013 Aug;62(8):2890-7. doi: 10.2337/db12-1802. Epub 2013 Apr 29.
PMID: 23630300RESULTHering BJ, Clarke WR, Bridges ND, Eggerman TL, Alejandro R, Bellin MD, Chaloner K, Czarniecki CW, Goldstein JS, Hunsicker LG, Kaufman DB, Korsgren O, Larsen CP, Luo X, Markmann JF, Naji A, Oberholzer J, Posselt AM, Rickels MR, Ricordi C, Robien MA, Senior PA, Shapiro AM, Stock PG, Turgeon NA; Clinical Islet Transplantation Consortium. Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia. Diabetes Care. 2016 Jul;39(7):1230-40. doi: 10.2337/dc15-1988. Epub 2016 Apr 18.
PMID: 27208344RESULTRicordi C, Goldstein JS, Balamurugan AN, Szot GL, Kin T, Liu C, Czarniecki CW, Barbaro B, Bridges ND, Cano J, Clarke WR, Eggerman TL, Hunsicker LG, Kaufman DB, Khan A, Lafontant DE, Linetsky E, Luo X, Markmann JF, Naji A, Korsgren O, Oberholzer J, Turgeon NA, Brandhorst D, Chen X, Friberg AS, Lei J, Wang LJ, Wilhelm JJ, Willits J, Zhang X, Hering BJ, Posselt AM, Stock PG, Shapiro AM, Chen X. National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities. Diabetes. 2016 Nov;65(11):3418-3428. doi: 10.2337/db16-0234. Epub 2016 Jul 27.
PMID: 27465220RESULTFoster ED, Bridges ND, Feurer ID, Eggerman TL, Hunsicker LG, Alejandro R; Clinical Islet Transplantation Consortium. Improved Health-Related Quality of Life in a Phase 3 Islet Transplantation Trial in Type 1 Diabetes Complicated by Severe Hypoglycemia. Diabetes Care. 2018 May;41(5):1001-1008. doi: 10.2337/dc17-1779. Epub 2018 Mar 21.
PMID: 29563196DERIVEDSenior PA, Bellin MD, Alejandro R, Yankey JW, Clarke WR, Qidwai JC, Schwieger TR, Eggerman TL, Robien MA, Rickels MR; Clinical Islet Transplantation Consortium. Consistency of quantitative scores of hypoglycemia severity and glycemic lability and comparison with continuous glucose monitoring system measures in long-standing type 1 diabetes. Diabetes Technol Ther. 2015 Apr;17(4):235-42. doi: 10.1089/dia.2014.0289. Epub 2015 Jan 28.
PMID: 25629445DERIVEDGala-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)
Study Officials
- STUDY CHAIR
Bernhard Hering, MD
University of Minnesota
- STUDY CHAIR
Olle Korsgren, PhD
Uppsala University Hospital
- STUDY CHAIR
Ali Naji, PhD
University of Pennsylvania
- STUDY CHAIR
Camillo Ricordi, MD
University of Miami
- STUDY CHAIR
James Shapiro, MD, PhD
University of Alberta
- STUDY CHAIR
Andrew Posselt, MD, PhD
University of California, San Francisco
- STUDY CHAIR
Nicole Turgeon, MD
Emory University
- STUDY CHAIR
Xunrong Luo, MD, PhD
Northwestern Univerity
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 9, 2007
First Posted
February 13, 2007
Study Start
October 1, 2006
Primary Completion
September 1, 2012
Study Completion
May 1, 2014
Last Updated
July 17, 2019
Record last verified: 2019-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
- Time Frame
- The data is available. ImmPort is a long-term archive of clinical and mechanistic data.
- Access Criteria
- Register for ImmPort at: https://www.immport.org/registration and submit a rationale for the purpose of requesting study data access. ImmPort is a long-term archive of clinical and mechanistic data, a National Institute of Allergy and Infectious Diseases Division of Allergy, Immunology and Transplantation (NIAID DAIT)-funded data repository. This archive is in support of the NIH mission to share data with the public. Data shared through ImmPort is provided by NIH-funded programs, other research organizations and individual scientists, ensuring these discoveries will be the foundation of future research.
Participant level data access and additional relevant materials are available to researchers and the public at: https://www.immport.org/home. The study Identifier in ImmPort is SDY1178.