Cardiomyopathy in Steroid-resistant Nephrotic Syndrome: Impact of Focal Segmental Glomerulosclerosis

This study has been terminated.
(study stopped due to lack of activity)
Sponsor:
Information provided by (Responsible Party):
North Shore Long Island Jewish Health System
ClinicalTrials.gov Identifier:
NCT00883636
First received: April 17, 2009
Last updated: June 18, 2013
Last verified: June 2013
  Purpose

The objective of this study is as follows:

  • Perform genetic analysis to define the prevalence of each of the known gene mutations in an unselected cohort of patients with focal segmental glomerulosclerosis (FSGS)
  • Perform a comprehensive assessment of cardiovascular status to determine the incidence of any cardiac abnormalities in patients with FSGS
  • Determine if patients with mutations in specific proteins are more likely to have cardiovascular abnormalities
  • Initiate long-term follow up in all patients to determine whether cardiac prognosis is related to any specific genetic abnormality

Condition Intervention
Focal Segmental Glomerulosclerosis
Nephrotic Syndrome
Steroid Resistant Nephrotic Syndrome
Chronic Kidney Disease
Other: Cardiovascular Assessment
Other: Renal Assessment
Other: Genetic Evaluation

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Cardiomyopathy in Steroid-resistant Nephrotic Syndrome: Impact of Focal Segmental Glomerulosclerosis

Resource links provided by NLM:


Further study details as provided by North Shore Long Island Jewish Health System:

Primary Outcome Measures:
  • Presence or Absence of any of the podocin gene mutations [ Time Frame: baseline ] [ Designated as safety issue: No ]

    Presence or Absence of any of the podocin gene mutations

    1. podocin gene (NPHS2)
    2. CD2-associated protein (CD2AP)
    3. actinin-4 (ACTN4)
    4. Nephrotic syndrome steroid-resistant gene (SRN1)
    5. Wilms Tumor 1(WT1)
    6. Transient receptor potential cation channel, subfamily C, member 6 (TRPC6)
    7. Phospholipase C-E1 (PLCE-1)


Biospecimen Retention:   Samples With DNA

Blood Serum, plasma


Enrollment: 4
Study Start Date: October 2008
Study Completion Date: October 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Focal Segmental Glomerulosclerosis Other: Cardiovascular Assessment
Measure of BNP, and Pro-BNP Complete 2 Dimensional Echocardiogram with Doppler evaluation including determination of, Left Ventricular mass, Ejection fraction, Midwall fractional shortening, velocity of early and late diastolic transmitral flow, and measurement of E/A ratio, Ratio of end-systolic wall stress to rate corrected velocity of circumferential fiber shortening.
Other: Renal Assessment
Complete a metabolic panel, CMP. Calculation of glomerular filtration rate, GFR, measure of urinary total protein, albumin and creatinine excretion in a first morning urine sample, 24 hour blood pressure monitoring,
Other: Genetic Evaluation
All patients will undergo genetic screening for all known podocyte gene mutations.
Non-Focal Segmental Glomerulosclerosis Other: Cardiovascular Assessment
Measure of BNP, and Pro-BNP Complete 2 Dimensional Echocardiogram with Doppler evaluation including determination of, Left Ventricular mass, Ejection fraction, Midwall fractional shortening, velocity of early and late diastolic transmitral flow, and measurement of E/A ratio, Ratio of end-systolic wall stress to rate corrected velocity of circumferential fiber shortening.
Other: Renal Assessment
Complete a metabolic panel, CMP. Calculation of glomerular filtration rate, GFR, measure of urinary total protein, albumin and creatinine excretion in a first morning urine sample, 24 hour blood pressure monitoring,
Other: Genetic Evaluation
All patients will undergo genetic screening for all known podocyte gene mutations.

Detailed Description:

Nephrotic Syndrome is a frequent cause of chronic kidney disease in children. Patients who are unresponsive to treatment with corticosteroids are further categorized as having steroid resistant nephrotic syndrome (SRNS). Renal biopsy in SRNS patients often reveal the histological lesion of focal segmental glomerulosclerosis (FSGS).

Genetic research has identified mutations in specific podocyte proteins, which may lead to the development of steroid resistant nephrotic syndrome. In addition to being expressed in the fetal adult kidney, human podocin mRNA is also expressed in the fetal heart tissue. Multiple case reports have described an association between cardiac abnormalities and familial FSGS. These findings suggest that this gene may be involved in the pathogenesis of cardiac abnormalities seen in this population.

The objectives of this study is to:

  • Perform genetic analysis to define the prevalence of each of the known podocyte gene mutations in an unselected cohort of patients with FSGS
  • Perform a comprehensive assessment of cardiovascular status to determine the incidence of any cardiac abnormalities in patients with FSGS
  • Determine if patients with mutations in specific podocyte proteins are more likely to have cardiovascular abnormalities
  • Initiate long-term follow up in all patients to determine whether cardiac prognosis is related to any specific genetic abnormality
  Eligibility

Ages Eligible for Study:   6 Months to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Focal Segmental Glomerulosclerosis Patients and Non Focal Segmental Glomerulosclerosis SRNS patients

Criteria

Inclusion Criteria:

  • Age 6 months - 21 years
  • SRNS, defined as failure to achieve remission in proteinuria after 4-6 weeks of daily steroid therapy in accord with ISKDC guidelines
  • GFR > 30 ml/min/1.73 m^2
  • Renal disease diagnosed based on kidney biopsy

Exclusion Criteria:

  • Secondary FSGS
  • Prior renal transplantation
  • Congenital extra-renal abnormalities
  • Significant structural cardiac abnormalities
  • pulmonary, hematologic, malignancy, or immune-related disease
  • inability to maintain adequate follow-up
  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: NCT00883636

Locations
United States, New York
Schneider Children's Hospital
New Hyde Park, New York, United States, 11040
Sponsors and Collaborators
North Shore Long Island Jewish Health System
Investigators
Principal Investigator: Deborah Mensch, M.D. North Shore LIJ Health System
  More Information

No publications provided

Responsible Party: North Shore Long Island Jewish Health System
ClinicalTrials.gov Identifier: NCT00883636     History of Changes
Other Study ID Numbers: GCRC 0245, IRB# 08-163
Study First Received: April 17, 2009
Last Updated: June 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by North Shore Long Island Jewish Health System:
Podocyte Protein
Podocyte Mutation

Additional relevant MeSH terms:
Glomerulosclerosis, Focal Segmental
Kidney Diseases
Nephrotic Syndrome
Renal Insufficiency, Chronic
Cardiomyopathies
Glomerulonephritis
Nephritis
Urologic Diseases
Nephrosis
Renal Insufficiency
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 21, 2014