- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00156364
Studies of Organ Transplantation in Animals and Man
"Ii-Pancreas Transplantation in Man", "Long Term Effects of Cyclosporine (CSA) and Tacrolimus (FK506) on Renal Structure and Function", "Studies of the Renal Interstitium Type I Diabetic Patients",
A. To study the effects of pancreas transplantation (PT) on the structural abnormalities of diabetic nephropathy (DN) in patients with type 1 (insulin-dependent) diabetes mellitus (type 1 D). These studies will address the influence of long-term normoglycemia on two stages of diabetic renal disease.
Due to the difficulties encountered for recruitment of patients to agree to undergo a GFR and a native kidney biopsy in conjunction with their clinical evaluation visit for transplant, we are now focusing efforts on obtaining skin biopsies previous to transplant, and then at regular intervals (3, 6, and 9 months, and yearly) following a successful transplantation.
- Pancreas Transplantation Alone (PTA). To determine, at 5, 10, and 15 years after PTA, the effects of normoglycemia on the established lesions of DN in the long-term type 1 D patients' own kidneys.
- Islet Transplantation Alone (ITA). To determine, at 5 years after ITA, the effects of normoglycemia on the early lesions of DN in type 1 D patients' own kidneys.
- Pancreas Transplantation after Kidney Transplantation (PAK). To determine at 5-10 years the effects of normoglycemia on the early structural lesions of DN in kidneys transplanted some years earlier into type 1 D recipients.
Hypothesis: The benefits of PT on the early glomerular lesions of DN will be demonstrable after 5 years in kidneys exposed to diabetes for a short duration, while in patients with long-standing type 1 D and more advanced glomerular DN lesions, longer exposure to euglycemia is necessary to demonstrate arrest or regression of the lesions.
Descripción general del estudio
Estado
Condiciones
Descripción detallada
Tipo de estudio
Inscripción (Actual)
Contactos y Ubicaciones
Ubicaciones de estudio
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Minnesota
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Minneapolis, Minnesota, Estados Unidos, 55455
- Universtity of Minnesota, Department of Pediatric Nephrology
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Descripción
Inclusion Criteria:
- Pancreas Transplantation. The patients considered for recruitment are those being evaluated for pancreas transplant alone or pancreas transplant after kidney transplantation in IDDM patients at the University of Minnesota (U of M). The consent forms have been approved by the Institutional Review Board at the University of Minnesota and the transplant coordinators responsible for interacting with patients have continuously utilized these consent forms in the recruitment process.
- Long-Term Post Kidney Transplant IDDM Patients. These patients are recruited by a study coordinator working directly with the PI and also use consent forms approved by the Institutional Review Board at the University of Minnesota.
Exclusion Criteria:
Pancreas Transplantation Alone
- Serum creatinine >1.5 mg/dl or CCr <50 ml/min/1.73M2, as kidneys in such IDDM patients are approaching end stage renal disease and are not readily amenable to morphometric analysis.
- Solitary kidneys or evidence of unilateral renal disease, based upon significant discrepancies in renal size by ultrasound.
- Evidence of other important kidney disease by history, ultrasound, or baseline biopsy.
- Other chronic diseases or conditions, in addition to IDDM, such as cystic fibrosis, serious mental illness, severe mental retardation, etc.
- Pregnancy. Pregnancy tests will be performed on all eligible females of child-bearing age, and pregnant women will be excluded. Patients will again be eligible 3 months after completion of pregnancy.
Pancreas Transplantation After Kidney Transplantation
- Serum creatinine >2 mg/dl; a higher value is accepted than for native kidney patients since patients have a single kidney and are receiving CSA or FK506.
- Moderate to severe chronic rejection on baseline biopsy.
- Evidence of other important kidney disease by history, ultrasound, or baseline biopsy.
- Other chronic diseases or conditions, in addition to IDDM, such as cystic fibrosis, serious mental illness, severe mental retardation, etc.
- Pregnancy. Pregnancy tests will be performed on all eligible females of child-bearing age, and pregnant women will be excluded. Patients will again be eligible 3 months after completion of pregnancy.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Structural-functional relationships in diabetic nephropathy through detailed quantitative studies of Podocytes.
Periodo de tiempo: baseline through follow-up biopsy
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structural-functional relationships in diabetic nephropathy through detailed quantitative studies of podocytes, including cell number, shape and attachment using innovative approaches including quantitative immunoelectron microscopy and 3-dimensional high resolution electron microscopy.
We will also study relationship between podocyte and glomerulotubular junction abnormalities.
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baseline through follow-up biopsy
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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We will continue our study the natural history of diabetic nephropathy.
Periodo de tiempo: Baseline through follow up visits
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We will study the structural parameters associated with urinary albumin excretion and determine which structural parameters are predictors of developing diabetic nephropathy.
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Baseline through follow up visits
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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We have compared the development of calcineurin lesions in the native kidneys of 14 tacrolimus- and 12 calcineurin-treated pancreas transplant alone recipients cured of type 1 diabetes.
Periodo de tiempo: Baseline through follow-up
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To avoid the pitfalls of renal allograft studies, including rejection and disease recurrence, we compared the development of calcineurin lesions in the native kidneys of 14 tacrolimus- and 12 calcineurin-treated pancreas transplant alone recipients cured of type 1 diabetes. Results: The cyclosporine and tacrolimus groups had, respectively, on average, 33% versus 44% decline in GFR (ns), 27% versus 29% increase in cortical interstitial fractional volume (ns), 245% versus 347% increase in the fractional volume of cortical tubules that were atrophic (ns), and 291% versus 392% increase in the percent of globally sclerotic glomeruli (ns). Arteriolar hyalinosis did not change significantly in either group. |
Baseline through follow-up
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Michael S Mauer, MD, Pediatric Nephrology, University of Minnesota
- Director de estudio: Arthur J Matas, MD, University of MN, School of Medicine, Dept of Surgery
Publicaciones y enlaces útiles
Publicaciones Generales
- Huang C, Kim Y, Caramori ML, Fish AJ, Rich SS, Miller ME, Russell GB, Mauer M. Cellular basis of diabetic nephropathy: II. The transforming growth factor-beta system and diabetic nephropathy lesions in type 1 diabetes. Diabetes. 2002 Dec;51(12):3577-81. doi: 10.2337/diabetes.51.12.3577.
- Sutherland DE, Gruessner RW, Dunn DL, Matas AJ, Humar A, Kandaswamy R, Mauer SM, Kennedy WR, Goetz FC, Robertson RP, Gruessner AC, Najarian JS. Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg. 2001 Apr;233(4):463-501. doi: 10.1097/00000658-200104000-00003.
- Moriya T, Groppoli TJ, Kim Y, Mauer M. Quantitative immunoelectron microscopy of type VI collagen in glomeruli in type I diabetic patients. Kidney Int. 2001 Jan;59(1):317-23. doi: 10.1046/j.1523-1755.2001.00493.x.
- Caramori ML, Kim Y, Huang C, Fish AJ, Rich SS, Miller ME, Russell G, Mauer M. Cellular basis of diabetic nephropathy: 1. Study design and renal structural-functional relationships in patients with long-standing type 1 diabetes. Diabetes. 2002 Feb;51(2):506-13. doi: 10.2337/diabetes.51.2.506. Erratum In: Diabetes 2002 Apr;51(4):1294.
- Katz A, Caramori ML, Sisson-Ross S, Groppoli T, Basgen JM, Mauer M. An increase in the cell component of the cortical interstitium antedates interstitial fibrosis in type 1 diabetic patients. Kidney Int. 2002 Jun;61(6):2058-66. doi: 10.1046/j.1523-1755.2002.00370.x.
- Suzuki D, Yagame M, Kim Y, Sakai H, Mauer M. Renal in situ hybridization studies of extracellular matrix related molecules in type 1 diabetes mellitus. Nephron. 2002;92(3):564-72. doi: 10.1159/000064110.
- Najafian B, Kim Y, Crosson JT, Mauer M. Atubular glomeruli and glomerulotubular junction abnormalities in diabetic nephropathy. J Am Soc Nephrol. 2003 Apr;14(4):908-17. doi: 10.1097/01.asn.0000057854.32413.81.
- Caramori ML, Fioretto P, Mauer M. Low glomerular filtration rate in normoalbuminuric type 1 diabetic patients: an indicator of more advanced glomerular lesions. Diabetes. 2003 Apr;52(4):1036-40. doi: 10.2337/diabetes.52.4.1036.
- Huang C, Kim Y, Caramori ML, Fish AJ, Rich SS, Miller ME, Russell GB, Mauer M. Cellular basis of diabetic nephropathy: III. In vitro GLUT1 mRNA expression and risk of diabetic nephropathy in type 1 diabetic patients. Diabetologia. 2004 Oct;47(10):1789-94. doi: 10.1007/s00125-004-1533-1. Epub 2004 Oct 22.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 8107M00116
- NIH 2P01-DK13083-38 (Otro número de subvención/financiamiento: NIH)
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