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Studies of Organ Transplantation in Animals and Man

10 de diciembre de 2014 actualizado por: Michael Mauer, MD

"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

Terminado

Condiciones

Descripción detallada

These continuation studies focus on large pancreas (PTx) and kidney (KTx) transplant populations of type 1 diabetic (D) patients (pts) in order to better understand diabetic nephropathy (DN), the leading cause of renal failure. Objectives are: (a) to determine whether PTx can more readily arrest or reverse the early vs. the more established lesions of DN; (b) to continue studies of renal structural-functional relationships in DN, with emphasis on the multifaceted pathologic DN lesions, including glomerular, vascular, interstitial lesions and glomerular-tubular connections; (c) to continue studies of DN natural history and the role of renal biopsy in predicting outcome; (d) to quantitate and understand the basis of atubular glomeruli (AG) in DN; (e) to elucidate glomerular (glom) epithelial cell abnormalities in DN; (f) to study the glom extracellular matrix abnormalities of DN; (g) to study the recurrence of DN in the KTx; (h) to study the molecular/genetic basis of DN and develop cellular markers of DN risk; (i) to determine the long-term (10-15 yr) structural consequences of cyclosporine (CSA) on the native kidneys of PTx recipients; and (j) to determine the shorter-term (5 yr) consequences of Prograf on the native kidneys of PTx recipients and compare these with those seen after 5 years of CSA treatment. Together, these studies will help to elucidate the pathogenesis and natural history of DN, unravel some of the molecular and genetic aspects of this disease, describe the dynamics of DN reversal in PTx pts, and recurrence in KTx pts and expand our knowledge of the nephrotoxic effects of calcinosis inhibitors.

Tipo de estudio

De observación

Inscripción (Actual)

655

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

    • Minnesota
      • Minneapolis, Minnesota, Estados Unidos, 55455
        • Universtity of Minnesota, Department of Pediatric Nephrology

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 60 años (Adulto)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Método de muestreo

Muestra de probabilidad

Población de estudio

This is not a study that recruits from the general population. This study is selectively offered to eligible patients who are scheduled for a Pre-pancreas Transplant evaluation visit at the University of Minnesota Medical Center, Fairview Transplant Center. If interested in learning more, contact the Transplant Center for more information.

Descripción

Inclusion Criteria:

  1. 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.
  2. 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

  1. 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.
  2. Solitary kidneys or evidence of unilateral renal disease, based upon significant discrepancies in renal size by ultrasound.
  3. Evidence of other important kidney disease by history, ultrasound, or baseline biopsy.
  4. Other chronic diseases or conditions, in addition to IDDM, such as cystic fibrosis, serious mental illness, severe mental retardation, etc.
  5. 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

  1. 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.
  2. Moderate to severe chronic rejection on baseline biopsy.
  3. Evidence of other important kidney disease by history, ultrasound, or baseline biopsy.
  4. Other chronic diseases or conditions, in addition to IDDM, such as cystic fibrosis, serious mental illness, severe mental retardation, etc.
  5. 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

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Structural-functional relationships in diabetic nephropathy through detailed quantitative studies of Podocytes.
Periodo de tiempo: baseline through follow-up biopsy
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.
baseline through follow-up biopsy

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
We will continue our study the natural history of diabetic nephropathy.
Periodo de tiempo: Baseline through follow up visits
We will study the structural parameters associated with urinary albumin excretion and determine which structural parameters are predictors of developing diabetic nephropathy.
Baseline through follow up visits

Otras medidas de resultado

Medida de resultado
Medida Descripción
Periodo de tiempo
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

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

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

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

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de enero de 1981

Finalización primaria (Actual)

1 de agosto de 2014

Finalización del estudio (Actual)

1 de agosto de 2014

Fechas de registro del estudio

Enviado por primera vez

7 de septiembre de 2005

Primero enviado que cumplió con los criterios de control de calidad

8 de septiembre de 2005

Publicado por primera vez (Estimar)

12 de septiembre de 2005

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

11 de diciembre de 2014

Última actualización enviada que cumplió con los criterios de control de calidad

10 de diciembre de 2014

Última verificación

1 de diciembre de 2014

Más información

Términos relacionados con este estudio

Otros números de identificación del estudio

  • 8107M00116
  • NIH 2P01-DK13083-38 (Otro número de subvención/financiamiento: NIH)

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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