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

James F. Markmann; Michael R. Rickels; Thomas L. Eggerman; Nancy D. Bridges; David E. Lafontant; Julie Qidwai; Eric Foster; William R. Clarke; Malek Kamoun; Rodolfo Alejandro; Melena D. Bellin; Kathryn Chaloner; Christine W. Czarniecki; Julia S. Goldstein; Bernhard J. Hering; Lawrence G. Hunsicker; Dixon B. Kaufman; Olle Korsgren; Christian P. Larsen; Xunrong Luo; Ali Naji; José Oberholzer; Andrew M. Posselt; Camillo Ricordi; Peter A. Senior; A. M.James Shapiro; Peter G. Stock; Nicole A. Turgeon

doi:10.1111/ajt.16174

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

James F. Markmann, Michael R. Rickels, Thomas L. Eggerman, Nancy D. Bridges, David E. Lafontant, Julie Qidwai, Eric Foster, William R. Clarke, Malek Kamoun, Rodolfo Alejandro, Melena D. Bellin, Kathryn Chaloner, Christine W. Czarniecki, Julia S. Goldstein, Bernhard J. Hering, Lawrence G. Hunsicker, Dixon B. Kaufman, Olle Korsgren, Christian P. Larsen, Xunrong LuoAli Naji, José Oberholzer, Andrew M. Posselt, Camillo Ricordi, Peter A. Senior, A. M.James Shapiro, Peter G. Stock, Nicole A. Turgeon

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56 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1477-1492
Number of pages	16
Journal	American Journal of Transplantation
Volume	21
Issue number	4
DOIs	https://doi.org/10.1111/ajt.16174
State	Published - Apr 2021

Bibliographical note

Funding Information:
Supported by grants from the National Institute of Allergy and Infectious Diseases and the National Institute for Diabetes and Digestive and Kidney Diseases to the following institutions: Emory University (U01AI089317), Northwestern University (U01AI089316), University of Alberta, Edmonton (U01AI065191), University of California San Francisco (U01DK085531), University of Illinois, Chicago (5U01DK070431), University of Iowa (U01DK070431), University of Miami (U01DK070460), University of Minnesota (U01AI065193), University of Pennsylvania (U01DK070430), and Uppsala University (U01AI065192). In addition, the study was supported by the following GCRC and CTSA awards to the following institutions: Emory University (UL1TR000454), Northwestern University (UL1RR025741 and UL1TR000150), University of California San Francisco (UL1TR000004), University of Illinois, Chicago (UL1TR000050), University of Miami (UL1TR000460), University of Minnesota, (M01‐RR000400 and UL1TR000114), and University of Pennsylvania (M01‐RR00040 and UL1TR000003). 1c

Publisher Copyright:
© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons

Keywords

basic (laboratory) research/science
clinical research/practice
diabetes
diabetes: type 1
islet transplantation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Markmann, J. F., Rickels, M. R., Eggerman, T. L., Bridges, N. D., Lafontant, D. E., Qidwai, J., Foster, E., Clarke, W. R., Kamoun, M., Alejandro, R., Bellin, M. D., Chaloner, K., Czarniecki, C. W., Goldstein, J. S., Hering, B. J., Hunsicker, L. G., Kaufman, D. B., Korsgren, O., Larsen, C. P., ... Turgeon, N. A. (2021). Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes. American Journal of Transplantation, 21(4), 1477-1492. https://doi.org/10.1111/ajt.16174

Markmann, JF, Rickels, MR, Eggerman, TL, Bridges, ND, Lafontant, DE, Qidwai, J, Foster, E, Clarke, WR, Kamoun, M, Alejandro, R, Bellin, MD, Chaloner, K, Czarniecki, CW, Goldstein, JS, Hering, BJ, Hunsicker, LG, Kaufman, DB, Korsgren, O, Larsen, CP, Luo, X, Naji, A, Oberholzer, J, Posselt, AM, Ricordi, C, Senior, PA, Shapiro, AMJ, Stock, PG & Turgeon, NA 2021, 'Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes', American Journal of Transplantation, vol. 21, no. 4, pp. 1477-1492. https://doi.org/10.1111/ajt.16174

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abstract = "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 HbA1c ≤ 6.5% or reduced by ≥ 1 percentage point at 1 year posttransplant. Median HbA1c 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.",

keywords = "basic (laboratory) research/science, clinical research/practice, diabetes, diabetes: type 1, islet transplantation",

author = "Markmann, {James F.} and Rickels, {Michael R.} and Eggerman, {Thomas L.} and Bridges, {Nancy D.} and Lafontant, {David E.} and Julie Qidwai and Eric Foster and Clarke, {William R.} and Malek Kamoun and Rodolfo Alejandro and Bellin, {Melena D.} and Kathryn Chaloner and Czarniecki, {Christine W.} and Goldstein, {Julia S.} and Hering, {Bernhard J.} and Hunsicker, {Lawrence G.} and Kaufman, {Dixon B.} and Olle Korsgren and Larsen, {Christian P.} and Xunrong Luo and Ali Naji and Jos{\'e} Oberholzer and Posselt, {Andrew M.} and Camillo Ricordi and Senior, {Peter A.} and Shapiro, {A. M.James} and Stock, {Peter G.} and Turgeon, {Nicole A.}",

note = "Funding Information: Supported by grants from the National Institute of Allergy and Infectious Diseases and the National Institute for Diabetes and Digestive and Kidney Diseases to the following institutions: Emory University (U01AI089317), Northwestern University (U01AI089316), University of Alberta, Edmonton (U01AI065191), University of California San Francisco (U01DK085531), University of Illinois, Chicago (5U01DK070431), University of Iowa (U01DK070431), University of Miami (U01DK070460), University of Minnesota (U01AI065193), University of Pennsylvania (U01DK070430), and Uppsala University (U01AI065192). In addition, the study was supported by the following GCRC and CTSA awards to the following institutions: Emory University (UL1TR000454), Northwestern University (UL1RR025741 and UL1TR000150), University of California San Francisco (UL1TR000004), University of Illinois, Chicago (UL1TR000050), University of Miami (UL1TR000460), University of Minnesota, (M01‐RR000400 and UL1TR000114), and University of Pennsylvania (M01‐RR00040 and UL1TR000003). 1c Publisher Copyright: {\textcopyright} 2020 The American Society of Transplantation and the American Society of Transplant Surgeons",

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T1 - Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes

AU - Markmann, James F.

AU - Rickels, Michael R.

AU - Eggerman, Thomas L.

AU - Bridges, Nancy D.

AU - Lafontant, David E.

AU - Qidwai, Julie

AU - Foster, Eric

AU - Clarke, William R.

AU - Kamoun, Malek

AU - Alejandro, Rodolfo

AU - Bellin, Melena D.

AU - Chaloner, Kathryn

AU - Czarniecki, Christine W.

AU - Goldstein, Julia S.

AU - Hering, Bernhard J.

AU - Hunsicker, Lawrence G.

AU - Kaufman, Dixon B.

AU - Korsgren, Olle

AU - Larsen, Christian P.

AU - Luo, Xunrong

AU - Naji, Ali

AU - Oberholzer, José

AU - Posselt, Andrew M.

AU - Ricordi, Camillo

AU - Senior, Peter A.

AU - Shapiro, A. M.James

AU - Stock, Peter G.

AU - Turgeon, Nicole A.

N1 - Funding Information: Supported by grants from the National Institute of Allergy and Infectious Diseases and the National Institute for Diabetes and Digestive and Kidney Diseases to the following institutions: Emory University (U01AI089317), Northwestern University (U01AI089316), University of Alberta, Edmonton (U01AI065191), University of California San Francisco (U01DK085531), University of Illinois, Chicago (5U01DK070431), University of Iowa (U01DK070431), University of Miami (U01DK070460), University of Minnesota (U01AI065193), University of Pennsylvania (U01DK070430), and Uppsala University (U01AI065192). In addition, the study was supported by the following GCRC and CTSA awards to the following institutions: Emory University (UL1TR000454), Northwestern University (UL1RR025741 and UL1TR000150), University of California San Francisco (UL1TR000004), University of Illinois, Chicago (UL1TR000050), University of Miami (UL1TR000460), University of Minnesota, (M01‐RR000400 and UL1TR000114), and University of Pennsylvania (M01‐RR00040 and UL1TR000003). 1c Publisher Copyright: © 2020 The American Society of Transplantation and the American Society of Transplant Surgeons

PY - 2021/4

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N2 - 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 HbA1c ≤ 6.5% or reduced by ≥ 1 percentage point at 1 year posttransplant. Median HbA1c 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.

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KW - clinical research/practice

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KW - diabetes: type 1

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

Abstract

Bibliographical note

Keywords

UN SDGs

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