Diabetologia · 2026
A multi-centre study of belatacept and sirolimus for islet transplantation.
СтатьяМногоцентровое исследованиеКлиническое исследование II фазыНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Rogers Natasha M, Hu Min, Jimenez-Vera Elvira, Gabor Hugh, Sharma Preeti P, Etherton Colleen, Loudovaris Tom, Hawthorne Wayne J, Drogemuller Chris J, Torpy David J, Holmes-Walker Deborah J, Gloss Brian, Grey Shane T, Goodman David, Coates P Toby, Kay Tom W, O'Connell Philip J, Australian Islet Consortium
Аннотация
AIMS/HYPOTHESIS: Islet transplantation is an appropriate treatment for selected individuals with type 1 diabetes mellitus and hypoglycaemia unawareness. The gold standard of maintenance immunosuppression to prevent allograft rejection is calcineurin inhibitor-based therapy; however, side effects warrant exploration of alternative immunosuppression. The co-stimulatory blocker belatacept and the mammalian target of rapamycin inhibitor sirolimus have demonstrated clinical benefit in solid organ transplantation, but efficacy in human islet transplantation is unknown.
METHODS: We conducted a non-randomised, phase 2, multi-centre, open-label clinical study. Participants with type 1 diabetes receiving at least one islet transplant were treated with belatacept/sirolimus (bela/siro) and compared with a contemporaneous cohort treated with tacrolimus/mycophenolate mofetil (tac/MMF). The primary outcome was freedom from hypoglycaemia, with positive C-peptide and HbA1c <53 mmol/mol (7.0%) at 12 months after the first transplant. Secondary outcomes included metabolic control (Igls criteria, BETA-2 score), allosensitisation and changes in peripheral blood immune cell populations.
RESULTS: Nine participants with type 1 diabetes received bela/siro, compared with 24 receiving tac/MMF. Eight participants (89%) receiving bela/siro achieved the primary outcome compared with 12 (52%) from the tac/MMF cohort. HbA1c, HYPO score and insulin requirements were reduced in both groups, although renal function remained unchanged only in the bela/siro group. Immunosuppression resulted in sustained suppression of all monocyte, NK, T and B cell subsets, although CD4+FOXP3+ regulatory T cell proportions were higher in the bela/siro group.
CONCLUSIONS/INTERPRETATION: Baseline immunosuppression with bela/siro facilitated early islet engraftment and rates of insulin independence, with less impact on renal function, supporting the rationale for routine use in islet transplantation.
TRIAL REGISTRATION: ANZCTR.org.au ACTRN12619000268145.
METHODS: We conducted a non-randomised, phase 2, multi-centre, open-label clinical study. Participants with type 1 diabetes receiving at least one islet transplant were treated with belatacept/sirolimus (bela/siro) and compared with a contemporaneous cohort treated with tacrolimus/mycophenolate mofetil (tac/MMF). The primary outcome was freedom from hypoglycaemia, with positive C-peptide and HbA1c <53 mmol/mol (7.0%) at 12 months after the first transplant. Secondary outcomes included metabolic control (Igls criteria, BETA-2 score), allosensitisation and changes in peripheral blood immune cell populations.
RESULTS: Nine participants with type 1 diabetes received bela/siro, compared with 24 receiving tac/MMF. Eight participants (89%) receiving bela/siro achieved the primary outcome compared with 12 (52%) from the tac/MMF cohort. HbA1c, HYPO score and insulin requirements were reduced in both groups, although renal function remained unchanged only in the bela/siro group. Immunosuppression resulted in sustained suppression of all monocyte, NK, T and B cell subsets, although CD4+FOXP3+ regulatory T cell proportions were higher in the bela/siro group.
CONCLUSIONS/INTERPRETATION: Baseline immunosuppression with bela/siro facilitated early islet engraftment and rates of insulin independence, with less impact on renal function, supporting the rationale for routine use in islet transplantation.
TRIAL REGISTRATION: ANZCTR.org.au ACTRN12619000268145.