Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes.

Autor: Markmann JF; Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Rickels MR; Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA., Eggerman TL; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA., Bridges ND; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Lafontant DE; Clinical Trials Statistical and Data Management Center, University of Iowa, Iowa City, Iowa, USA., Qidwai J; Clinical Trials Statistical and Data Management Center, University of Iowa, Iowa City, Iowa, USA., Foster E; Ferring Pharmaceuticals, Parsippany, New Jersey, USA., Clarke WR; Clinical Trials Statistical and Data Management Center, University of Iowa, Iowa City, Iowa, USA., Kamoun M; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Alejandro R; Diabetes Research Institute and Clinical Cell Transplant Program, University of Miami Miller School of Medicine, Miami, Florida, USA., Bellin MD; Department of Endocrinology, University of Minnesota, Minneapolis, Minnesota, USA., Chaloner K; Clinical Trials Statistical and Data Management Center, University of Iowa, Iowa City, Iowa, USA., Czarniecki CW; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Goldstein JS; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Hering BJ; Schulze Diabetes Institute and Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA., Hunsicker LG; Clinical Trials Statistical and Data Management Center, University of Iowa, Iowa City, Iowa, USA., Kaufman DB; Division of Transplantation, Department of Surgery, University of Wisconsin, Madison, Wisconsin, USA., Korsgren O; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden., Larsen CP; Emory Transplant Center, Emory University, Atlanta, Georgia, USA., Luo X; Department of Medicine, Duke University, Durham, North Carolina, USA., Naji A; Division of Transplantation, Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA., Oberholzer J; Department of Surgery, University of Illinois, Chicago, Illinois, USA., Posselt AM; Department of Surgery, University of California, San Francisco, California, USA., Ricordi C; Diabetes Research Institute and Clinical Cell Transplant Program, University of Miami Miller School of Medicine, Miami, Florida, USA., Senior PA; Clinical Islet Transplant Program and Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada., Shapiro AMJ; Clinical Islet Transplant Program and Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada., Stock PG; Department of Surgery, University of California, San Francisco, California, USA., Turgeon NA; Department of Surgery, University of Texas Dell Medical School, Austin, Texas, USA.
Jazyk: angličtina
Zdroj: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2021 Apr; Vol. 21 (4), pp. 1477-1492. Date of Electronic Publication: 2020 Aug 09.
DOI: 10.1111/ajt.16174
Abstrakt: Allogeneic islet transplant offers a minimally invasive option for β cell replacement in the treatment of type 1 diabetes (T1D). The CIT consortium trial of purified human pancreatic islets (PHPI) in patients with T1D after kidney transplant (CIT06), a National Institutes of Health-sponsored phase 3, prospective, open-label, single-arm pivotal trial of PHPI, was conducted in 24 patients with impaired awareness of hypoglycemia while receiving intensive insulin therapy. PHPI were manufactured using standardized processes. PHPI transplantation was effective with 62.5% of patients achieving the primary endpoint of freedom from severe hypoglycemic events and HbA 1c  ≤ 6.5% or reduced by ≥ 1 percentage point at 1 year posttransplant. Median HbA 1c declined from 8.1% before to 6.0% at 1 year and 6.3% at 2 and 3 years following transplant (P < .001 for all vs baseline), with related improvements in hypoglycemia awareness and glucose variability. The improved metabolic control was associated with better health-related and diabetes-related quality of life. The procedure was safe and kidney allograft function remained stable after 3 years. These results add to evidence establishing allogeneic islet transplant as a safe and effective treatment for patients with T1D and unstable glucose control despite intensive insulin treatment, supporting the indication for PHPI in the post-renal transplant setting.
(© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)
Databáze: MEDLINE
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