The Nephrotic Syndrome Study Network (NEPTUNE)

Kidney Disease Clinical Trial

Official title:

The Nephrotic Syndrome Study Network (NEPTUNE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01240564
• Other study ID #: 110023
• Secondary ID: 11-DK-0023
• Status: Recruiting
• Phase: N/A
• First received: November 11, 2010
• Last updated: November 11, 2014
• Start date: October 2010

Study information

• Verified date: February 2014
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Anaida Widell
• Phone: (301) 451-9946
• Email: awidell[@]cc.nih.gov
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

Background:

• The Nephrotic Syndrome Study Network (NEPTUNE) is a network of multidisciplinary researchers who are investigating why kidney disease happens. NEPTUNE researchers will collect kidney tissue and other samples (for example, blood and urine) from individuals who are scheduled to have kidney biopsies to determine the cause of protein in the urine (only one kidney biopsy is necessary).

Objectives:

• To collect kidney tissue, other samples, and data /information for continuing research into kidney diseases.

Eligibility:

• Individuals at least 18 years of age who need to have a kidney biopsy to determine the cause of protein in the urine, do not have a systemic disease that is the cause of the their kidney disease, and have not received specific treatment for kidney disease.

Design:

• This study involves a screening and baseline visit and additional followup visits after the kidney biopsy.

• Participants will be screened with a medical history and physical examination, as well as blood and urine samples and collection of fingernail clippings. Participants will also complete questionnaires about their history of kidney problems.

• During the kidney biopsy, performed at the NIH Clinical Center, researchers will take an additional tissue sample for research.

• Participants will return for followup visits at NIH every 4 months in the first year, and every 6 months in the second through fifth years after the biopsy. Additional blood and urine samples will be collected at each visit, and fingernail clippings will also be collected annually by the study researchers.

• Treatment for kidney disease will not be provided as part of this protocol and instead will generally be provided by the patient s own physician.

Compensation:

Subjects received compensation for each visit to the NIH Clinical Center.

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 (1). 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

• INCLUSION CRITERIA

Inclusion Criteria for the FSGS/MCD Cohort

• A new diagnosis of FSGS or MCD according to characteristic light, electron (EM), and immunofluorescence microscopy (IM), with presence of at least five glomeruli per biopsy available for analysis. Biopsy slides will be reviewed and diagnosis confirmed by 2 study pathologists according to standardized criteria developed by the pathology committee;

• Documented urinary protein excretion greater than or equal to 500 mg/24 hours or spot protein: creatinine ratio equivalent at the time of diagnosis or within 3 months of the screening/eligibility visit.

Inclusion criteria for the MN Cohort

• A new diagnosis of MN according to characteristic light, electron (EM), and immunofluorescence microscopy (IM), with presence of diagnostic changes in at least one glomerulus per biopsy. Biopsy slides will be reviewed and diagnosis confirmed by 2 study pathologists according to standardized criteria developed by the pathology committee

• Documented urinary protein excretion greater than or equal to 500 mg/24 hours or spot protein: creatinine ratio equivalent at the time of diagnosis or within 3 months of the screening/eligibility visit.

Inclusion criteria for the OG Cohort

• A new diagnosis of glomerulopathy according to characteristic light, electron (EM), and immunofluorescence microscopy (IM), with presence of diagnostic changes in at least one glomerulus per biopsy. Biopsy slides will be reviewed and diagnosis confirmed by 2 study pathologists according to standardized criteria developed by the pathology committee;

• Documented urinary protein excretion greater than or equal to 500 mg/24 hours or spot protein:creatinine ratio equivalent at the time of diagnosis or within 3 months of the screening/eligibility visit.

EXCLUSION CRITERIA

Exclusion criteria for the FSGS/MCD and MN Cohorts

• Prior solid organ transplant

• A clinical diagnosis of FSGS/MCD or MN 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

• Clinical or histological evidence of other renal diseases (Alport, Nail Patella, Diabetic Nephropathy, IgA-nephritis, monoclonal gammopathy (multiple myelomas), genito-urinary malformations with vesico-uretheral reflux or renal dysplasia)

• Known systemic disease diagnosis at time of enrollment with 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)

• Laboratory information unavailable prior to consent and biopsy procedure subsequently supporting exclusion criteria will deem a participant ineligible.

Exclusion Criteria for the Other Glomerulopathies

• 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

• Clinical or histological evidence of other renal diseases (Alport, Nail Patella, Diabetic Nephropathy, IgA-nephritis, monoclonal gammopathy (multiple myelomas), genito-urinary malformations with vesico-uretheral 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)

• Laboratory information unavailable prior to consent and biopsy procedure subsequently supporting exclusion criteria will deem a participant ineligible.

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Glomerular Disease
• Glomerulonephritis
• Glomerulosclerosis, Focal
• Glomerulosclerosis, Focal Segmental
• Kidney Disease
• Kidney Diseases
• Nephrosis
• Nephrotic Syndrome
• Syndrome

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Ellis EN, Martz K, Talley L, Ilyas M, Pennington KL, Blaszak RT. Factors related to long-term renal transplant function in children. Pediatr Nephrol. 2008 Jul;23(7):1149-55. doi: 10.1007/s00467-008-0779-0. Epub 2008 Feb 27. — View Citation

Schnaper HW. Primary nephrotic syndrome of childhood. Curr Opin Pediatr. 1996 Apr;8(2):141-7. Review. — View Citation

Tune BM, Mendoza SA. Treatment of the idiopathic nephrotic syndrome: regimens and outcomes in children and adults. J Am Soc Nephrol. 1997 May;8(5):824-32. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1) Event rate of change in urinary proteinuria excretion. 2) Rate of change in renal function: 25mls/min/1.73m2 reduction, 50% decline in follow-up eGFR, end stage renal disease.
Secondary	1) Quality of life2) New Onset Diabetes

External Links

•   NIH Clinical Center Detailed Web Page