Evidence map›Paper›PMID 27208344›Full record

Trial reportDiabetes care2016

Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia.

Bernhard J Hering, William R Clarke, Nancy D Bridges, Thomas L Eggerman, Rodolfo Alejandro, Melena D Bellin, Kathryn Chaloner, Christine W Czarniecki, Julia S Goldstein, Lawrence G Hunsicker and 16 more

2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetes care, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 322 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
322citing papers in PubMed, 1 pooled it
71.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00434811 phase3completednot on this map

Islet Transplantation in Type 1 Diabetes

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2006 to 2014Enrolled48ConditionsType 1 Diabetes MellitusArmsAllogeneic Pancreatic Islet Cells, Antithymocyte Globulin, Sirolimus, Tacrolimus, Etanercept
NCT05973734 phase1enrolling by invitationnot on this mapstarted 2024, after this paper: background citation

Clinical Islet Transplantation With Apheresis, Isolation and Reintroduction of Recipient Regulatory T Cells or Administration of Deceased Donor Vertebral Bone Marrow in Type 1 Diabetes

TypeinterventionalSponsorStanford UniversityRan2024 to 2030Enrolled24ConditionsIslet TransplantationArmsInfusion of recipient T regulatory cell, Infusion of concomitant Donor Derived Vertebral Bone Marrow
3 · Its place in the literature

Who cites it

322 citing papers in PubMed, 1 synthesis or guideline pooled it, 631 citations in OpenAlex.

  1. Impact of Islet Transplantation on Type 1 Diabetes-Related Complication: A Systematic Review.Transplant international : official journal of the European Society for Organ Transplantation · 2025
    Pooled it
  2. Trial
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  5. Feasibility and efficacy of combined pancreatic islet-lung transplantation in cystic fibrosis-related diabetes-PIM study: A multicenter phase 1-2 trial.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022
    Trial
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  7. Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021
    Trial
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262 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 14 institutions in 3 countries.

Bernhard J HeringSchulze Diabetes Institute and Department of Surgery, University of Minnesota, Minneapolis, MN.
William R ClarkeClinical Trials Statistical and Data Management Center, University of Iowa, Iowa City, IA bhering@umn.edu.
Nancy D BridgesNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Thomas L EggermanNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
Rodolfo AlejandroDiabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL.
Melena D BellinSchulze Diabetes Institute and Department of Pediatrics, University of Minnesota, Minneapolis, MN.
Kathryn ChalonerClinical Trials Statistical and Data Management Center, University of Iowa, Iowa City, IA.
Christine W CzarnieckiNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Julia S GoldsteinNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Lawrence G HunsickerClinical Trials Statistical and Data Management Center, University of Iowa, Iowa City, IA.
Dixon B KaufmanDivision of Transplantation, Department of Surgery, University of Wisconsin, Madison, WI.
Olle KorsgrenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Christian P LarsenEmory Transplant Center, Emory University, Atlanta, GA.
Xunrong LuoComprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL.
James F MarkmannDivision of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Ali NajiInstitute for Diabetes, Obesity and Metabolism and Departments of Surgery and Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Jose OberholzerDivision of Transplantation, University of Illinois Hospital and Health Sciences System, Chicago, IL.
Andrew M PosseltDepartment of Surgery, University of California, San Francisco, San Francisco, CA.
Michael R RickelsInstitute for Diabetes, Obesity and Metabolism and Departments of Surgery and Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Camillo RicordiDiabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL.
Mark A RobienNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Peter A SeniorClinical Islet Transplant Program and Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
A M James ShapiroClinical Islet Transplant Program and Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Peter G StockDepartment of Surgery, University of California, San Francisco, San Francisco, CA.
Nicole A TurgeonEmory Transplant Center, Emory University, Atlanta, GA.
Clinical Islet Transplantation Consortium
National Institute of Allergy and Infectious Diseases · USUniversity of Iowa · USEmory University · USNational Institutes of Health · USUniversity of Alberta · CAUniversity of California, San Francisco · USUniversity of Miami · USUniversity of Minnesota · USUniversity of Pennsylvania · USHarvard University · USNorthwestern University · USUniversity of Illinois Chicago · USUniversity of Wisconsin–Madison · USUppsala University · SE

Funding

Immune Tolerance NetworkUM1AI109565 · NIAID · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2022 to 2025
$94.0M
WOMEN'S HEALTH IN CYSTIC FIBROSISM01RR000400 · UNIVERSITY OF MINNESOTA TWIN CITIES · 1985 to 2005
$19.6M
ZDV VS ZDV + DDL VS ZDV + DDL + NVP IN ASYMPTOMATIC HIV PATIENTSM01RR000040 · UNIVERSITY OF PENNSYLVANIA · 1985 to 2005
$19.2M
Clinical Islet Transplantation: Data Coordinating CenterU01DK070431 · UNIVERSITY OF IOWA · 2004 to 2004
$9.6M
Strategies to Improve Long Term Islet Graft SurvivalU01DK070460 · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2004 to 2005
$6.8M
Advancing Islet Transplants for Type 1 Diabetes CareU01AI065193 · UNIVERSITY OF MINNESOTA TWIN CITIES · 2004 to 2005
$6.8M
B-Lymphocyte Immunotherapy in Islet TransplantationU01DK070430 · UNIVERSITY OF PENNSYLVANIA · 2004 to 2005
$6.2M
Islet Transplant - Costimulatory Blockade with LEA29YU01AI065191 · UNIVERSITY OF ALBERTA · 2004 to 2005
$5.6M
Innate immunity in clinical islet transplantationU01AI065192 · UPPSALA UNIVERSITY · 2004 to 2005
$4.6M
IMMUNE TOLERANCE NETWORK-266015416N01AI015416 · REGENTS OF THE UNIVERSITY OF C · 2002 to 2005
–
NCATS NIH HHS UL1 TR000003NCATS NIH HHS UL1 TR000004NCATS NIH HHS UL1 TR000050NCATS NIH HHS UL1 TR000114NCATS NIH HHS UL1 TR000150NCATS NIH HHS UL1 TR000454NCATS NIH HHS UL1 TR000460NCRR NIH HHS M01 RR000040NCRR NIH HHS M01 RR000400NCRR NIH HHS UL1 RR025741NIAID NIH HHS N01 AI015416NIAID NIH HHS U01 AI065191NIAID NIH HHS U01 AI065192NIAID NIH HHS U01 AI065193NIAID NIH HHS U01 AI089316NIAID NIH HHS U01 AI089317NIAID NIH HHS UM1 AI109565NIDDK NIH HHS U01 DK070430NIDDK NIH HHS U01 DK070431NIDDK NIH HHS U01 DK070460NIDDK NIH HHS U01 DK085531
6 · The paper itself

Abstract

objectiveImpaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50-80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment. RESEARCH DESIGN AND

methodsThis multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA1c <7.0% (53 mmol/mol) at day 365 and freedom from SHEs from day 28 to day 365 after the first transplant.

resultsThe primary end point was successfully met by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA1c level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients.

conclusionsTransplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.

Indexed as

AdultBlood GlucoseC-PeptideDiabetes Mellitus, Type 1FemaleGlycated HemoglobinHumansHypoglycemiaImmunosuppression TherapyIslets of Langerhans TransplantationMaleMiddle AgedNorth AmericaYoung AdultBlood GlucoseC-PeptideGlycated Hemoglobinhemoglobin A1c protein, human

Identifiers

PMID27208344
PMCPMC5317236
OpenAlexW2341414956

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.