Studies of Organ Transplantation in Animals and Man
2014年12月10日 更新者：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.
調査の概要
状態
完了
条件
詳細な説明
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.
研究の種類
観察的
入学 (実際)
655
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Minnesota
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Minneapolis、Minnesota、アメリカ、55455
- Universtity of Minnesota, Department of Pediatric Nephrology
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～60年 (大人)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
サンプリング方法
確率サンプル
調査対象母集団
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.
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Structural-functional relationships in diabetic nephropathy through detailed quantitative studies of Podocytes.
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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We will continue our study the natural history of diabetic nephropathy.
時間枠：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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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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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.
時間枠：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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
協力者
捜査官
- 主任研究者：Michael S Mauer, MD、Pediatric Nephrology, University of Minnesota
- スタディディレクター：Arthur J Matas, MD、University of MN, School of Medicine, Dept of Surgery
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
1981年1月1日
一次修了 (実際)
2014年8月1日
研究の完了 (実際)
2014年8月1日
試験登録日
最初に提出
2005年9月7日
QC基準を満たした最初の提出物
2005年9月8日
最初の投稿 (見積もり)
2005年9月12日
学習記録の更新
投稿された最後の更新 (見積もり)
2014年12月11日
QC基準を満たした最後の更新が送信されました
2014年12月10日
最終確認日
2014年12月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。