Nephrotic Syndrome Study Network (NEPTUNE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by University of Michigan
Sponsor:
Collaborators:
The NephCure Foundation
Information provided by (Responsible Party):
Matthias Kretzler, University of Michigan
ClinicalTrials.gov Identifier:
NCT01209000
First received: July 29, 2010
Last updated: April 30, 2013
Last verified: April 2013
  Purpose

Minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and Membranous nephropathy (MN), generate an enormous individual and societal financial burden, accounting for approximately 12% of prevalent end stage renal disease (ESRD) cases (2005) at an annual cost in the US of more than $3 billion. However, the clinical classification of these diseases is widely believed to be inadequate by the scientific community. Given the poor understanding of MCD/FSGS and MN biology, it is not surprising that the available therapies are imperfect. The therapies lack a clear biological basis, and as many families have experienced, they are often not beneficial, and in fact may be significantly toxic. Given these observations, it is essential that research be conducted that address these serious obstacles to effectively caring for patients.

In response to a request for applications by the National Institutes of Health, Office of Rare Diseases (NIH, ORD) for the creation of Rare Disease Clinical Research Consortia, a number of affiliated universities joined together with The NephCure Foundation the NIDDK, the ORDR, and the University of Michigan in collaboration towards the establishment of a Nephrotic Syndrome (NS) Rare Diseases Clinical Research Consortium.

Through this consortium the investigators hope to understand the fundamental biology of these rare diseases and aim to bank long-term observational data and corresponding biological specimens for researchers to access and further enrich.


Condition
Minimal Change Disease (MCD)
Membranous Nephropathy
Glomerulosclerosis, Focal Segmental

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Nephrotic Syndrome Study Network Under the Rare Diseases Clinical Research Network

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Event rate of change in urinary protein excretion and renal function. [ Time Frame: 60 months ] [ Designated as safety issue: No ]
    Defined as remission, partial remission and non-remission

  • Rate of change in renal function. [ Time Frame: 60 months ] [ Designated as safety issue: No ]

    Defined as:

    1. 25 mls/min/1.73m2 reduction in follow-up estimated GFR (using the 4-variable MDRD equation for ages ≥18 years and modified Schwartz for ages <18 years) compared to baseline estimated GFR
    2. 50% decline in follow-up estimated GFR compared to baseline measurement
    3. End stage renal disease defined as estimated GFR ≤10cc/min, initiation of maintenance dialysis or preemptive kidney transplantation.


Secondary Outcome Measures:
  • Quality of Life: [ Time Frame: 60 months ] [ Designated as safety issue: No ]
    Patient-reported outcome will be assessed using Quality of Life questionnaires at regular intervals as stipulated in the visit calendar using the SF-36, PedsQL and the Patient Reported Outcome Measurement Information System (PROMIS) (in the age-appropriate groups).

  • Malignancies [ Time Frame: 60 months ] [ Designated as safety issue: No ]
    Any cancer diagnosis of the skin, hematopoietic system, or solid organ after enrollment in NEPTUNE

  • Infections, Serious and Systemic [ Time Frame: 60 months ] [ Designated as safety issue: No ]

    Infections including one of the following:

    1. Documented diagnosis of infection of the skin or subcutaneous tissue (e.g. cellulitis), vascular system, peritoneum, or any vital organ requiring the use of parenteral antibiotics and/or oral antibiotics alone or in combination for a treatment interval of ≥72 hours.
    2. Hospitalization for treatment of infection

  • Thromboembolic Events [ Time Frame: 60 months ] [ Designated as safety issue: No ]

    Documented diagnosis of one of the following:

    1. Embolic cerebrovascular accident
    2. Deep venous thrombosis
    3. Renal vein thrombosis or
    4. Pulmonary embolus

  • Hospitalization [ Time Frame: 60 months ] [ Designated as safety issue: No ]
    Documented hospital admission, including observation for ≥24 hours.

  • Emergency Department/ Observation Unit Visit [ Time Frame: 60 months ] [ Designated as safety issue: No ]
    Documented visit to an emergency department or observation unit that does not lead to hospitalization and is less than 24 hours.

  • Acute Kidney Injury [ Time Frame: 60 months ] [ Designated as safety issue: No ]
    Documented diagnosis of acute kidney injury as defined by the AKIN (Mehta et al., Critical Care 2007, 11:R31) and/or renal failure requiring renal replacement therapy <3 months.

  • Death [ Time Frame: 60 months ] [ Designated as safety issue: No ]
    1. Documentation of death that is secondary to infection or sepsis.
    2. Cardiovascular/Cerebrovascular-related Death: Sudden death; Myocardial infarction; Congestive heart failure; Primary intractable serious arrhythmia; Peripheral vascular disease; Ischemic cerebrovascular accident; Hemorrhagic cerebrovascular accident; Thromboembolic event
    3. Documentation of death secondary to cancer
    4. Other Death: Documentation of death that does not fall into the above categories.

  • New Onset Diabetes [ Time Frame: 60 months ] [ Designated as safety issue: No ]

    Diagnosis of diabetes as indicated by 1 or more of the following not present at NEPTUNE Enrollment:

    1. Documented diagnosis of diabetes in medical record
    2. Casual (non-fasting) blood glucose > 200 mg/dL c) Fasting blood glucose > 126 mg/dL d) 2 hour glucose > 200 after oral glucose tolerance test e) chronic use (>6 mos) hypoglycemic therapy outside of pregnancy f) Hemogloblin A1C >= 6.5%


Biospecimen Retention:   Samples With DNA

Renal tissue core (from clinically indicated kidney biopsy procedure) Blood products Urine products DNA/RNA specimens (declining consent does not forego participant eligibility) Finger/toe nail clippings


Estimated Enrollment: 600
Study Start Date: April 2010
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
FSGS/MCD Cohort

Focal Segmental Glomerulosclerosis/Minimal Change Disease (FSGS/MCD) Cohort

Participants enrolled in NEPTUNE with a biopsy proven histological diagnosis for FSGS or MCD.

MN Cohort

Membranous Nephropathy (MN) Cohort

Enrolled participants, biopsy proven to have membranous nephropathy.

Other glomerulopathies cohort
Participants enrolled in NEPTUNE and determined to not have FSGS/MCD or MN will be followed in a third group.

Detailed Description:

Idiopathic Nephrotic Syndrome (NS) is a rare disease syndrome responsible for approximately 12% of all causes of end-stage kidney disease (ESRD) and up to 20% of ESRD in children. Treatment strategies for Focal and Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD) and Membranous Nephropathy (MN), the major causes of NS, include high dose prolonged steroid therapy, cyclophosphamide, cyclosporine A, tacrolimus, mycophenolate mofetil and other immunosuppressive agents, which all carry significant side effects. Failure to obtain remission using the current treatment approaches frequently results in progression to ESRD with its associated costs, morbidities, and mortality. In the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry, half of the pediatric patients with Steroid Resistant Nephrotic Syndrome required renal replacement therapy within two years of being enrolled in the disease registry. FSGS also has a high recurrence rate following kidney transplantation (30-40%) and is the most common recurrent disease leading to allograft loss.

The prevailing classification of Nephrotic Syndrome categorizes patients into FSGS, MCD, and MN, if in the absence of other underlying causes, glomerular histology shows a specific histological pattern. This classification does not adequately predict the heterogeneous natural history of patients with FSGS, MCD, and MN. Major advances in understanding the pathogenesis of FSGS and MCD have come over the last ten years from the identification of several mutated genes responsible for causing Steroid Resistant Nephrotic Syndrome (SRNS) presenting with FSGS or MCD histopathology in humans and model organisms. These functionally distinct genetic disorders can present with indistinguishable FSGS lesions on histology confirming the presence of heterogeneous pathogenic mechanisms under the current histological diagnoses.

The limited understanding of FSGS, MCD, and MN biology in humans has necessitated a descriptive classification system in which heterogeneous disorders are grouped together. This invariably consigns these heterogeneous patients to the same therapeutic approaches, which use blunt immunosuppressive drugs that lack a clear biological basis, are often not beneficial, and are complicated by significant toxicity. The foregoing shortcomings make a strong case that concerted and innovative investigational strategies combining basic science, translational, and clinical methods should be employed to study FSGS, MCD, and MN. It is for these reasons that the Nephrotic Syndrome Study Network is established to conduct clinical and translational research in patients with FSGS/MCD and MN.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Adult patients with signs and symptoms of kidney disease consistent with FSGS, MCD, MN or proteinuric renal disease or pediatric participants not previously biopsied, who present for patient care at the participating clinical centers will be the primary study population targeted for enrollment into the NEPTUNE study. Potential participants willing to receive their biopsy care, and subsequent follow-up study visits at one of these sites are also welcome to participate.

Criteria

Inclusion Criteria:

Patients presenting with an incipient clinical diagnosis for FSGS/MCD or MN or pediatric participants not previously biopsied, with a clinical diagnosis for FSGS/MCD or MN meeting the following inclusion criteria:

  • Documented urinary protein excretion ≥500 mg/24 hours or spot protein: creatinine ratio equivalent at the time of diagnosis or within 3 months of the screening/eligibility visit.
  • Scheduled renal biopsy

Exclusion Criteria:

  • Prior solid organ transplant
  • A clinical diagnosis of glomerulopathy without diagnostic renal biopsy
  • Clinical, serological or histological evidence of systemic lupus erythematosus (SLE) as defined by the ARA criteria. Patients with membranous in combination with SLE will be excluded because this entity is well defined within the International Society of Nephrology/Renal Pathology Society categories of lupus nephritis, and frequently overlaps with other classification categories of SLE nephritis (68)
  • Clinical or histological evidence of other renal diseases (Alport, Nail Patella, Diabetic Nephropathy, IgA-nephritis, monoclonal gammopathy (multiple myelomas), genito-urinary malformations with vesico-urethral reflux or renal dysplasia)
  • Known systemic disease diagnosis at time of enrollment with a life expectancy less than 6 months
  • Unwillingness or inability to give a comprehensive informed consent
  • Unwillingness to comply with study procedures and visit schedule
  • Institutionalized individuals (e.g., prisoners)
  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: NCT01209000

Contacts
Contact: Chrysta C. Lienczewski, BS 1-877-9-NEPTUNE NEPTUNE-Study@umich.edu
Contact: Denise L. Taylor-Moon, BA 1-877-9-NEPTUNE NEPTUNE-Study@umich.edu

  Show 34 Study Locations
Sponsors and Collaborators
University of Michigan
The NephCure Foundation
Investigators
Principal Investigator: Matthias Kretzler, MD University of Michigan
  More Information

Additional Information:
No publications provided

Responsible Party: Matthias Kretzler, Professor, University of Michigan
ClinicalTrials.gov Identifier: NCT01209000     History of Changes
Other Study ID Numbers: 6801, 1U54DK083912
Study First Received: July 29, 2010
Last Updated: April 30, 2013
Health Authority: Canada: Ethics Review Committee
United States: Institutional Review Board

Keywords provided by University of Michigan:
Focal and Segmental Glomerulosclerosis
Focal & Segmental Glomerulosclerosis
Focal Segmental Glomerulosclerosis
FSGS
Minimal change disease
MCD
Membranous Nephropathy
MN
Nephrotic Syndrome
Neph Syndrome
NEPTUNE
NephCure
Halpin

Additional relevant MeSH terms:
Glomerulonephritis, Membranous
Glomerulosclerosis, Focal Segmental
Kidney Diseases
Nephrosis, Lipoid
Nephrotic Syndrome
Glomerulonephritis
Nephritis
Urologic Diseases
Autoimmune Diseases
Immune System Diseases
Nephrosis

ClinicalTrials.gov processed this record on August 21, 2014