Nephrotic Syndrome Study Network

Membranous Nephropathy Clinical Trial

— NEPTUNE  

Official title:

Nephrotic Syndrome Study Network Under the Rare Diseases Clinical Research Network

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01209000
• Other study ID #: 6801
• Secondary ID: 1U54DK083912
• Status: Recruiting
• Start date: April 2010
• Est. completion date: June 30, 2026

Study information

• Verified date: May 2024
• Source: University of Michigan
• Contact: Chrysta C. Lienczewski, BS
• Phone: 734-615-5021
• Email: NEPTUNE-Study[@]umich.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT01240564

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 80 Years

Eligibility

Cohort A (biopsy cohort) 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 =1500 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

Cohort B (non-biopsy, cNEPTUNE) Inclusion Criteria:

• Age <19 years of age

• Initial presentation with <30 days immunosuppression therapy

• Proteinuria/nephrotic

• UA>2+ and edema OR

• UA>2+ and serum albumin <3 OR

• UPC > 2g/g and serum albumin <3

Exclusion Criteria (Cohort A&B):

• 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)

Related Conditions & MeSH terms

• Glomerulonephritis, Membranous
• Glomerulosclerosis, Focal Segmental
• Kidney Diseases
• Membranous Nephropathy
• Minimal Change Disease (MCD)
• Nephrosis
• Nephrosis, Lipoid
• Nephrotic Syndrome
• Syndrome

Intervention

Procedure:
• Kidney Biopsy
Patients scheduled to undergo a clinically indicated kidney biopsy will be requested to consent to an additional renal core, to be set aside until all clinical care is complete.

Locations

Country	Name	City	State
Canada	York Central Hospital	Richmond Hill	Ontario
Canada	Scarborough Hospital	Scarborough	Ontario
Canada	Credit Valley Hospital	Toronto	Ontario
Canada	Sunnybrook Hospital	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
United States	CS Mott Children's Hospital, University of Michigan	Ann Arbor	Michigan
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Emory University and Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	University of Colorado Anschutz School of Medicine	Aurora	Colorado
United States	Johns Hopkins Medical Institute	Baltimore	Maryland
United States	Kidney Disease Section, NIDDK, NIH	Bethesda	Maryland
United States	Montefiore Medical Center	Bronx	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Atrium Health Levine Children's Hospital	Charlotte	North Carolina
United States	John Stroger Cook County Hospital	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	MetroHealth Hospital at Case Western Medical Center	Cleveland	Ohio
United States	University Hospital Rainbow Babies & Children's Hospital	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	University of Texas-Southwestern	Dallas	Texas
United States	Texas Children's Hospital - Baylor College of Medicine	Houston	Texas
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Southern California-Children's Hospital	Los Angeles	California
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Cohen Children's Hospital	New Hyde Park	New York
United States	Bellevue Hospital	New York	New York
United States	Columbia University Medical Center	New York	New York
United States	New York University Medical Center	New York	New York
United States	New York University Veterans Administration	New York	New York
United States	Stanford University School of Medicine	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Temple University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University - St Louis	Saint Louis	Missouri
United States	University of California San Francisco Benioff Children's Hospitals	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	University of Washington	Seattle	Washington
United States	Providence Medical Research Center	Spokane	Washington
United States	Lundquist Biomedical Research Institute at Harbor UCLA Medical Center	Torrance	California
United States	Wake Forest School of Medicine	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
University of Michigan	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), The NephCure Foundation

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event rate of change in urinary protein excretion and renal function.	Defined as remission, partial remission and non-remission	60 months
Primary	Rate of change in renal function.	Defined as: 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; 50% decline in follow-up estimated GFR compared to baseline measurement; End stage renal disease defined as estimated GFR =10cc/min, initiation of maintenance dialysis or preemptive kidney transplantation.	60 months
Secondary	Quality of Life:	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).	60 months
Secondary	Malignancies	Any cancer diagnosis of the skin, hematopoietic system, or solid organ after enrollment in NEPTUNE	60 months
Secondary	Infections, Serious and Systemic	Infections including one of the following: 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.; Hospitalization for treatment of infection	60 months
Secondary	Thromboembolic Events	Documented diagnosis of one of the following: Embolic cerebrovascular accident; Deep venous thrombosis; Renal vein thrombosis or; Pulmonary embolus	60 months
Secondary	Hospitalization	Documented hospital admission, including observation for =24 hours.	60 months
Secondary	Emergency Department/ Observation Unit Visit	Documented visit to an emergency department or observation unit that does not lead to hospitalization and is less than 24 hours.	60 months
Secondary	Acute Kidney Injury	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.	60 months
Secondary	Death	Documentation of death that is secondary to infection or sepsis.; 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; Documentation of death secondary to cancer; Other Death: Documentation of death that does not fall into the above categories.	60 months
Secondary	New Onset Diabetes	Diagnosis of diabetes as indicated by 1 or more of the following not present at NEPTUNE Enrollment: Documented diagnosis of diabetes in medical record; 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%	60 months

External Links

•   Patient Advocacy group for FSGS/MCD
•   Patient advocacy group for MN
•   Rare Diseases Clinical Research Networks Homepage
•   The NEPTUNE Study Homepage