Studies of Organ Transplantation in Animals and Man

This study is currently recruiting participants.
Verified March 2013 by University of Minnesota - Clinical and Translational Science Institute
Sponsor:
Collaborators:
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute ( Michael Mauer, MD )
ClinicalTrials.gov Identifier:
NCT00156364
First received: September 7, 2005
Last updated: March 13, 2013
Last verified: March 2013
  Purpose

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.


Condition
Diabetes Mellitus

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: "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",

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Structural-functional relationships in diabetic nephropathy through detailed quantitative studies of Podocytes. [ Time Frame: baseline through follow-up biopsy ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • We will continue our study the natural history of diabetic nephropathy. [ Time Frame: Baseline through follow up visits ] [ Designated as safety issue: No ]
    We will study the structural parameters associated with urinary albumin excretion and determine which structural parameters are predictors of developing diabetic nephropathy.


Other Outcome Measures:
  • 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. [ Time Frame: Baseline through follow-up ] [ Designated as safety issue: No ]

    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.



Biospecimen Retention:   Samples With DNA

Skin Fibroblasts, Plasma and Serum samples, Urine samples, kidney biopsy culture samples.


Estimated Enrollment: 1000
Study Start Date: January 1981
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

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.

Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00156364

Contacts
Contact: Transplant Center , Fairview University Medical Center 612-625-5115 or 800-328-5465 tranplant-center@fairview.org
Contact: Karen Dalmacio, BS 624-9871 dalm0008@umn.edu

Locations
United States, Minnesota
Universtity of Minnesota, Department of Pediatric Nephrology Recruiting
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Michael Mauer, MD
Investigators
Principal Investigator: Michael S Mauer, MD Pediatric Nephrology, University of Minnesota
Study Director: Arthur J Matas, MD University of MN, School of Medicine, Dept of Surgery
  More Information

Publications:

Responsible Party: University of Minnesota - Clinical and Translational Science Institute ( Michael Mauer, MD )
ClinicalTrials.gov Identifier: NCT00156364     History of Changes
Other Study ID Numbers: 8107M00116, NIH 2P01-DK13083-38
Study First Received: September 7, 2005
Last Updated: March 13, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
Diabetic Nephropathy
Kidney Transplant
Pancreas Transplant
Renal Interstitium
Diabetes Mellitus
Cyclosporine
Tacrolimus

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Cyclosporins
Cyclosporine
Tacrolimus
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 17, 2014