Permeability Factor in Focal Segmental Glomerulosclerosis
2 other identifiers
interventional
15
1 country
1
Brief Summary
Focal segmental glomerulosclerosis (FSGS) is a renal syndrome characterized by proteinuria (usually nephrotic range), limited response to conventional therapy, and a poor renal prognosis, with progression to end stage renal failure in at least 50% of patients. As a syndrome, FSGS likely has many specific etiologies, only a few of which are well-defined. Recently, it has been suggested that some idiopathic FSGS patients have elevated circulating levels of a protein that induces glomerular permeability in vitro and in vivo. While there has been no consistent term for this factor, it will be termed here FSGS permeability factor (FPF). The purposes of the present study are five fold:
- 1.To identify a population of FSGS patients with elevated FPF levels
- 2.To examine RNA expression profiles of peripheral blood mononuclear cells (PBMC) in FSGS patients with elevated FPF levels
- 3.To define the kinetics of FPF disappearance and reappearance in FSGS patients receiving immunomodulatory therapy and in the case of patients with recurrent FSGS following renal transplant, those receiving plasma exchange
- 4.To identify immunosuppressive agents which are successful in inducing sustained reduction in FPF levels
- 5.To determine in patients with FSGS who are awaiting renal transplant, whether sustained reduction in FPF levels is associated with reduced risk of recurrent FSGS.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Dec 2000
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2000
CompletedFirst Submitted
Initial submission to the registry
December 22, 2000
CompletedFirst Posted
Study publicly available on registry
December 25, 2000
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2014
CompletedResults Posted
Study results publicly available
February 10, 2016
CompletedFebruary 10, 2016
February 1, 2016
13.5 years
December 22, 2000
June 19, 2015
February 8, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Reduction in Proteinuria in Recurrent FSGS Following Renal Transplant With Plasma Exchange and Cyclophosphamide.
Outcomes for FSGS occurring in native kidneys: A. Complete remission: proteinuria \<0.3 g/d ; B. Partial remission: proteinuria between 0.3 and 2 g/d ; C. Incomplete response: proteinuria between 2 and 3.5 g/d ; D. Relapse: return to proteinuria ≥3.5 g/d ; Note that counts within each category A-D may be summarized relative to remaining categories, as a proportion (relative to complement of the whole group count) with calculations implicitly based on zero/one valued binary variables, whose means are proportions, so to report 95% confidence intervals calculated using an exact binomial distribution.
every 3 months up to a year followed with native kidneys
Secondary Outcomes (4)
Comparison of RNA Expression Profiles in PBMC From Patients With FPF, Without FPF and Control Subjects
End of study
Define the Kinetics of FPF in FSGS Patients Receiving Immunomodulatory Therapy or Plasma Exchange.
End of study
Correlate the Effect of Immunosuppressive Agents Which Reduce Proteinuria in Recurrent FSGS With the Effect on FPF Levels
End of study
Determine Whether Renal Transplantation in Patients Whose Elevated FPF Levels Have Been Reduced for a Sustained Period is Associated With a Reduced Prevalence of Recurrent FSGS.
End of study
Study Arms (1)
Plasma Exchange + Cyclophosphamide
EXPERIMENTALProcedure/Surgery: Plasma exchange A course of plasma exchange of 5 treatments over 10 days, then administration of cyclophosphamide. Drug: Cyclophosphamide For GFR \> 50 ml/min/1.73 m2 received oral cyclophosphamide at a dose of 2 mg/kg/ day for 3 months. For GFR \< 50 ml/min/1.73 m2 but \> 10 ml/min/1.73 m2 will receive oral cyclophosphamide at a 25% reduced dose or 1.5 mg/kg/d for 3 months.
Interventions
A course of plasma exchange of 5 treatments over 10 days, then administration of cyclophosphamide.
For GFR \> 50 ml/min/1.73 m2 received oral cyclophosphamide at a dose of 2 mg/kg/ day for 3 months. For GFR \< 50 ml/min/1.73 m2 but \> 10 ml/min/1.73 m2 will receive oral cyclophosphamide at a 25% reduced dose or 1.5 mg/kg/d for 3 months.
Eligibility Criteria
You may qualify if:
- Patients with idiopathic focal segmental glomerulosclerosis on renal biopsy, including the following categories:
- A) Untreated FSGS
- B) Steroid-dependent FSGS
- C) Steroid resistant FSGS
- D) Recurrent FSGS, with functioning allograft
- E) FSGS in ESRD, receiving hemodialysis
- Adults greater than or equal to18 will be eligible for all studies.
- Children greater than 20 kilograms, will be eligible for all branches of the study except for treatment of steroid resistant FSGS with pirfenidone, as pirfenidone has not previously been administered to pediatric patients in any setting. Children less than 20 kilograms will be excluded from the study for the following reason: plasma exchange in patients less than 20 kilograms requires a red blood cell transfusion, which significantly increases the risk of the procedure by exposing the patient to the risk of transfusion associated infections, and the safety of an aggressive course of plasma exchange has not been established in this population.
You may not qualify if:
- Secondary FSGS: HIV-associated FSGS or hyperfiltration FSGS, including FSGS associated with congenital renal abnormalities, renal mass reduction, reflux nephropathy, interstitial nephritis, and sickle cell anemia are excluded.
- Patients with disease associated with immunosuppression, other than chronic renal failure.
- The presence of malignancy or the history of other serious, complicating illness such as myocardial infarction or cerebrovascular accident in the past six months, at the discretion of the investigators.
- For plasma exchange: A Department of Transfusion Medicine consultant will evaluate all potential plasma exchange patients. Those with prolonged PT, PTT, platelet count less than 100,000 or receiving anticoagulant therapy will undergo plasma exchange only if the consultant considers this to be safe.
- For prednisone: uncontrolled diabetes mellitus (requiring greater than 100 units of insulin/day with the concurrence of the Endocrinology consultant), active infection including hepatitis B or C (if that is the advice of the Hepatology consultant), infection with HIV (as these patients are at increased risk of avascular necrosis), other active infection (if that is the advice of the Infectious Disease consultant), history of avascular necrosis or bone densitometry indicating bone mass less than 2SD below normal, active ulcer disease, history of steroid-induced psychosis, morbid obesity, positive PPD or history of past positive PPD without adequate treatment are excluded.
- For Cyclophosphamide:
- A) Allergy or hypersensitivity to cyclophosphamide
- B) Leukocyte less than 3000 cells/microliter or ANC less than 1500 cells/microliter or evidence of bone marrow compromise
- C) Prior irradiation to the heart or therapy with doxorubicin or other cardiotoxic medication (may increase the risk for cardiotoxicity)
- D) Peritoneal dialysis, as there is no published evidence that cyclophosphamide metabolites can be safely removed.
- E) Certain drugs will be used with caution or avoided. Barbiturates and phenytoin induce the hepatic enzymes that metabolize cyclophosphamide and therefore if these medications are required, cyclophosphamide doses may need to be increased to achieve a comparable immunosuppressive effect. Drugs that inhibit cyclophosphamide metabolism include allopurinol, imipramine, and phenothiazines, chloramphenicol and chlorpromazine; these drugs will be avoided. NSAID increase the risk of hyponatremia; these drugs will be avoided.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892, United States
Related Publications (3)
Korbet SM. Primary focal segmental glomerulosclerosis. J Am Soc Nephrol. 1998 Jul;9(7):1333-40. doi: 10.1681/ASN.V971333. No abstract available.
PMID: 9644647BACKGROUNDCameron JS. Recurrent renal disease after renal transplantation. Curr Opin Nephrol Hypertens. 1994 Nov;3(6):602-7. doi: 10.1097/00041552-199411000-00007.
PMID: 7881983BACKGROUNDValeri A, Barisoni L, Appel GB, Seigle R, D'Agati V. Idiopathic collapsing focal segmental glomerulosclerosis: a clinicopathologic study. Kidney Int. 1996 Nov;50(5):1734-46. doi: 10.1038/ki.1996.493.
PMID: 8914044BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Note: definitive FSGS Permeability Factor (FPF) assays still in development. Data/samples transferred to the NIH-CC Glomerulosclerosis Consolidation protocol: focus on cardiotrophin like cytokine 1 \& antibodies to a panel of podocyte proteins as FPF.
Results Point of Contact
- Title
- Jeffrey B. Kopp, MD
- Organization
- National Institute of Diabetes & Digestive & Kidney Diseases
Study Officials
- PRINCIPAL INVESTIGATOR
Jeffrey B Kopp, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 22, 2000
First Posted
December 25, 2000
Study Start
December 1, 2000
Primary Completion
June 1, 2014
Study Completion
June 1, 2014
Last Updated
February 10, 2016
Results First Posted
February 10, 2016
Record last verified: 2016-02