Clinical Trial: Nephrotic Syndrome Study Network

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Nephrotic Syndrome Study Network Under the Rare Diseases Clinical Research Network

Brief Summary:

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.

Detailed Summary:

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 histol
Sponsor: University of Michigan

Current Primary Outcome:

• Event rate of change in urinary protein excretion and renal function. [ Time Frame: 60 months ]
  Defined as remission, partial remission and non-remission
• Rate of change in renal function. [ Time Frame: 60 months ]

  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.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Quality of Life: [ Time Frame: 60 months ]
  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 ]
  Any cancer diagnosis of the skin, hematopoietic system, or solid organ after enrollment in NEPTUNE
• Infections, Serious and Systemic [ Time Frame: 60 months ]

  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 ]

  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 ]
  Documented hospital admission, including observation for ≥24 hours.
• Emergency Department/ Observation Unit Visit [ Time Frame: 60 months ]
  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 ]
  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 ]
  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 ]

  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%

Original Secondary Outcome: Same as current

Information By: University of Michigan

Dates:
Date Received: July 29, 2010
Date Started: April 2010
Date Completion: June 2019
Last Updated: May 1, 2017
Last Verified: May 2017