Linkage Consortium for End-Stage Renal Disease

This study has been completed.
Sponsor:
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00301249
First received: March 9, 2006
Last updated: January 12, 2010
Last verified: January 2010
  Purpose

The Family Investigation of Nephropathy and Diabetes (FIND)Study is a multi-center consortium. The charge of the consortium is to acquire sets of families with well-characterized diabetic nephropathy, establish a secure master FIND database, and perform a genome scan to identify chromosomal regions linked with diabetic nephropathy.


Condition Phase
Diabetes
Diabetic Nephropathy
Phase 4

Study Type: Observational
Official Title: The Family Investigation of Nephropathy and Diabetes (FIND) Study

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Estimated Enrollment: 7000
Study Start Date: October 1999
Estimated Study Completion Date: November 2005
Detailed Description:

Diabetic Nephropathy (DN) is undoubtedly a multifactorial disease, and a large proportion of patients affected with either type 1 or type 2 diabetes develop diabetic nephropathy and progress to end stage renal disease (ESRD). When poor prognostic factors such as hypertension and chronic hyperglycemia are aggressively treated, the rate of progression of diabetic nephropathy can be slowed. However, no interventions have been shown to reliably halt the progression of diabetic nephropathy. Numerous studies have suggested that genetic predisposition to diabetic nephropathy exists, but genes for nephropathy have not yet been isolated. It is anticipated that a comprehensive analysis of a large number of uniformly phenotyped ESRD families will be necessary to isolate genes for ESRD. Such a database of families may not be available at any single institution. The FIND study has established a centralized Genetic Analysis and Data Coordinating Center (GADCC) that, together with eight participating investigation centers (PICs), three minority recruitment centers, and the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), will use the emerging high-throughput genetic technologies to enable identification of diabetic nephropathy susceptibility or protection genes. The charge of the consortium is to acquire sets of families with well-characterized diabetic nephropathy, establish a secure master FIND database, and perform a genome scan to identify chromosomal regions linked with diabetic nephropathy. The FIND study population includes participants from European American (EA), Native American (NA), African American (AA) and Mexican American (AA) populations.

Two analytic approaches are utilized in FIND. The Family Study approach involves the enrollment of probands, affected or discordant sibling and their affected family members. Analytic methods include affected sibling pair (ASP), discordant sibling pair (DSP) affected relative pair (ARP), and discordant relative pair (DRP) linkage analyses for the Family Study. The Mapping by Admixture and Linkage Disequilibrium (MALD) approach involves the enrollment of probands and a population based control for both the AA and MA studies. In addition, a spousal control (diad) and when available, a child 18 years or older, will be recruited (triad)for the AA MALD study only.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

For the Family protocol, proband must meet diagnostic criteria for diabetes and have nephropathy that meets one of the following:

  • diabetic nephropathy diagnosed from a kidney biopsy and a history of overt proteinuria.
  • ESRD considered due to diabetic nephropathy because
  • diabetes is present for ≥ 5 years prior to the initiation of renal replacement therapy and diabetic retinopathy has been diagnosed at any time; or
  • diabetes is present ≥ 5 years prior to the initiation of replacement therapy and either a 24 hour urine collection contains ≥ 3 gm protein/24 hours or a random urine protein (mg/dl)/ creatinine (mg/dl) ratio is ≥ 3.0; or
  • diabetic retinopathy is present and either a previous 24 hour urine collection contains ≥ 3 gm protein/24 hours or a random urine protein (mg/dl)/ creatinine (mg/dl) ratio is ≥ 3.0.
  • nephropathy without ESRD that is considered to be diabetic nephropathy because (a) diabetic retinopathy and a 24 hr urine collection with either ≥ 1 gram proteinuria/24 hours or a urine protein (mg/dl)/ creatinine (mg/dl) ratio ≥ 1.0; or (b) at a time when diabetes duration is ≥ 10 years, either a urine collection of ≥ 3 grams protein/24 hours or a urine protein (mg/dl) /creatinine (mg/dl) ratio ≥ 3.0.

African-American patients with chronic renal failure are as MALD cases by meeting criteria for diabetic nephropathy, as described for Family probands, or having nephropathy (serum creatinine ≥ 2.0 mg/dl) not due to diabetes or known monogenic renal disease. Mexican-Americans recruited as MALD cases must meet criteria for diabetic nephropathy as defined for the Family probands. Phenotype criteria for probands entered into the Family or MALD protocols must be confirmed by medical record review.

Eligibility of family members and MALD control subjects is based on laboratory tests obtained at the time of screening. Entry of a proband with diabetic nephropathy into the Family protocol also requires participation of either two living parents or at least one full sibling with diabetes. To be enrolled as having nephropathy, the diabetic sib must meet one of the following criteria:

  • renal biopsy consistent with a diagnosis of diabetic nephropathy;
  • urinary albumin excretion ≥ 30 mg/24hr or a urine albumin (mg/dl)/creatinine (mg/dl) ratio ≥ 0.03;
  • a serum creatinine concentration ≥ 1.6 mg/dl for men or ≥ 1.4 mg/dl for women; or
  • ESRD. Unaffected sibs are recruited if they have had diabetes for ≥ 10 years, have normal serum creatinine and albumin excretion (< 30 mg albumin/24 hours, or a urine albumin (mg/dl)/creatinine (mg/dl) ratio < 0.03) and no historical evidence of kidney disease.

The criteria for MALD control subjects differ by ethnic group. For the African-American MALD protocol, two different control samples are recruited. First, an adult offspring with or without renal disease and the other parent of the offspring, who cannot have evidence of renal disease, are collected as controls for African-American probands with either diabetic or non-diabetic nephropathy. Together with the probands, this forms a sample of triads (offspring and other parent) or dyads (spouse only). A second group of African-American control subjects consists of unrelated individuals with diabetes duration ≥ 10 years and without nephropathy (as defined above for diabetic sibs). For Mexican Americans, a single unrelated control population is recruited with diabetes duration ≥ 10 years but without nephropathy (as defined above for diabetic sibs).

Exclusion Criteria:

A. Did not sign the informed consent: refusal to participate. B. Diagnosis not confirmed. C. Appropriate siblings not available. D. Judged not likely or unable to follow study protocol. E. Ethnicity of parents or grandparent not suitable. F. Spouse not available.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00301249

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
University of California Los Angeles
Los Angeles, California, United States, 90024
Harbor-UCLA Medical Center
Torrance, California, United States, 90502
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21234
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Investigators
Principal Investigator: Sudha Iyengar, PhD Case Western Reserve University
Study Chair: Barry I Freedman, MD Wake Forest School of Medicine
Principal Investigator: Sharon Adler, MD University of California, Los Angeles
Principal Investigator: Hanna Abboud, MD University of Texas Health Sciences Center at San Antonio
Principal Investigator: John R Sedor, MD Case Western Reserve University
Principal Investigator: Rulan Parekh, MD Johns Hopkins University
Principal Investigator: Philip Zager, MD University of New Mexico
Principal Investigator: William Knowler, MD, PhD NIDDK-Phoenix
Principal Investigator: Susanne Nicholas, MD University of California, Los Angeles
Study Director: Rebekah Rasooly, PhD National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study Director: Paul Kimmel, MD National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00301249     History of Changes
Other Study ID Numbers: DK57292 (completed)
Study First Received: March 9, 2006
Last Updated: January 12, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Diabetes
Nephropathy
Diabetic Nephropathy
Genome Scan
Genetic Research

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetic Nephropathies
Kidney Diseases
Kidney Failure, Chronic
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Diabetes Complications
Renal Insufficiency, Chronic
Renal Insufficiency

ClinicalTrials.gov processed this record on July 24, 2014