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View Clinical Trial (Medical Research Study)
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Cause of Focal Segmental Glomerulosclerosis - NCT00001392-20892 (Clinical Trial 111171)
Permalink: http://www.ClinicalConnection.com/exp/ExpandedPatientViewStudy111171.aspx
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| City: |
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Bethesda |
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State:
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MD |
| Zip Code: |
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20892 |
| Conditions: |
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AIDS Associated Nephropathy - Focal Glomerulosclerosis - HIV Infections |
| Purpose: |
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The present protocol seeks to advance our understanding of glomerular diseases characterized
by progressive glomerulosclerosis in the absence of established immune-mediated renal
injury. To this end, we will enroll patients with primary podocytopathies (minimal change
nephropathy, focal segmental glomerulosclerosis, collapsing glomerulopathy) and diabetic
nephropathy, as well as patients with the clinical diagnosis (prior to renal biopsy) with
one of these conditions. The protocol has three modules, with two consents and two assents.
There is no ceiling on patient recruitment for modules 1 and 2. We want to recruit 16
patients for module 3.
1. EVALUATION AND TREATMENT OF GLOMERULOSCLEROSIS: This protocol will serve as a
screening protocol for specific treatment protocols. It will also allow us to provide
second opinions about selected glomerular diseases, to collect research samples (blood,
urine, and archival kidney tissue) and treat selected patients with renal disease using
standard therapy. These studies will allow us to test particular hypotheses and may
provide the opportunity to generate new hypotheses that could be tested in other
protocols.
2. RESEARCH RENAL BIOPSY IN PATIENTS WITH GLOMERULOSCLEROSIS: We will carry out renal
biopsy for research purposes (limited to previously-diagnosed collapsing
glomerulopathy) or to obtain additional renal tissue for research from a biopsy
performed for clinical indications (includes diagnosed or suspected minimal change
nephropathy, focal segmental glomerulosclerosis, collapsing glomerulopathy, diffuse
mesangial sclerosis, and diabetic nephropathy). This tissue will be used for studies
of the podocyte transcriptome, and other glomerular and tubular processes, and for
studies to identify viral causes of primary podocyte diseases.
3. Obesity-Associated Kidney Disease. We will collaborate with Dr. Mona Khurana in studies
of lean and obese young adults carried out at Children's National Medical Center. We
will assist her in the measurements of iothalamate and para-aminnohippurate clearance,
in order to determine glomerular filtration rate and renal plasma flow.
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| Study summary: |
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The present protocol seeks to advance our understanding of glomerular diseases characterized
by progressive glomerulosclerosis in the absence of established immune-mediated renal
injury. To this end, we will enroll patients with primary podocytopathies (minimal change
nephropathy, focal segmental glomerulosclerosis, collapsing glomerulopathy) and diabetic
nephropathy, as well as patients with the clinical diagnosis (prior to renal biopsy) with
one of these conditions. The protocol has four modules, with four consents and four
assents. There is no ceiling on patient recruitment for modules 1 and 2. We want to recruit
16 patients for module 3 and 20 patients for module 4.
1. EVALUATION AND TREATMENT OF GLOMERULOSCLEROSIS: This protocol will serve as a
screening protocol for specific treatment protocols. It will also allow us to provide
second opinions about selected glomerular diseases, to collect research samples (blood,
urine, and archival kidney tissue) and treat selected patients with renal disease using
standard therapy. These studies will allow us to test particular hypotheses and may
provide the opportunity to generate new hypotheses that could be tested in other
protocols.
2. RESEARCH RENAL BIOPSY IN PATIENTS WITH GLOMERULOSCLEROSIS: We will carry out renal
biopsy for research purposes (limited to previously-diagnosed collapsing
glomerulopathy) or to obtain additional renal tissue for research from a biopsy
performed for clinical indications (includes diagnosed or suspected minimal change
nephropathy, focal segmental glomerulosclerosis, collapsing glomerulopathy, diffuse
mesangial sclerosis, and diabetic nephropathy). This tissue will be used for studies
of the podocyte transcriptome, and other glomerular and tubular processes, and for
studies to identify viral causes of primary podocyte diseases.
3. OBESITY-ASSOCIATE KIDNEY DISEASE. We will collaborate with Dr. Mona Khurana in studies
of lean and obese young adults carried out at Children's National Medical Center. We
will assist her in the measurements of iothalamate and para-aminnohippurate clearance,
in order to determine glomerular filtration rate and renal plasma flow.
4. PILOT STUDY OF RITUXIMAB PLUS CYCLOSPORINE IN FSGS. We will test this combination
therapy in an open label phase 2 study involving up to 20 subjects who have failed to
maintain a sustained remission first-line therapy with glucocorticoids or who have a
compelling contraindication to the use of flucocorticoids, including diabetes mellitus,
morbid obesity, or patient choice.; patients may also have failed one or more
additional immunosuppressive therapies. Therapy will involve up to two courses of
rituximab and approximately 48 weeks of cyclosporine, followed by a taper. |
| Criteria: |
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- Module 1: EVALUATION AND TREATMENT OF GLOMERULOSCLEROSIS
INCLUSION CRITERIA:
Children of all ages and adults, including pregnant women, and impaired subjects, all with
kidney disease. For pathogenetic studies, we will also include healthy volunteers,
including children greater than 12 yrs of age and adults.
EXCLUSION CRITERIA:
None
Module 2: RESEARCH RENAL BIOPSY
1. Clinically-indicated renal biopsy, with use of a portion of a second biopsy core for
research.
INCLUSION CRITERIA:
All adults or children with past renal biopsy which demonstrated a glomerulosclerotic
disease or in all adults or children without prior renal biopsy and clinical
suspicion of glomerulosclerotic disease.
EXCLUSION CRITERIA;
Pregnant women.
2. Clinically-indicated renal biopsy, obtaining a third biopsy core for research
purposes.
INCLUSION CRITERIA:
All adults with past renal biopsy which demonstrated a glomerulosclerotic disease or
in all adult patients without prior renal biopsy and high pre-test likelihood of a
glomerulosclerotic disease.
EXCLUSION CRITERIA:
Pregnant women, patients with a single kidney, impaired subjects, and children less
than 18 yr.
3. Research renal biopsy, performed largely or exclusively for research purposes.
INCLUSION CRITERIA:
Adults with collapsing glomerulopathy.
EXCLUSION CRITERIA:
Pregnant women, patients with a single kidney, impaired subjects, and children less
than 18 yr.
Module 3: RENAL FUNCTION AND STRUCTURE IN LEAN, OVERWEIGHT, AND OBESE YOUNG ADULTS
INCLUSION CRITERIA:
Young adults aged 18 to 21, including lean young adults with BMI less than 25 kg/m2
and obese young adults with BMI greater than 30 kg/m2. Participants with a history of
hyperlipidemias or high fasting glucose will still be eligible for the study as these
co-morbidities are often consequence of being obese.
EXCLUSION CRITERIA:
Young adults with proteinuria (random urine protein to creatinine ratio greater than
0.2, microalbuminuria (spot urine albumin to cretinine ratio greater than 20 mg/g),
creatinine clearance less than 80 mL/min/1.73m2, chronic kidney disease, high blood
pressure (systolic blood pressure greater than 140 and diastolic blood pressure
greater than 90 on 3 blood pressure readings obtained at least one week apart),
diabetes, and pregnant women.
Module 4: PILOT STUDY OF RITUXIMAB AND CYCLOSPORINE
INCLUSION CRITERIA: (Up to 20 patients)
Inclusion criteria for adult patients:
- Estimated average proteinuria > 3.5 g/d despite optimal use of an ACE inhibitor
or ARB (or possibly both), last dose increase at least 4 weeks before qualifying
proteinuria determination
- Women must use reliable birth control method to avoid pregnancy while
participating in the study.
- Patients who have failed to respond with a complete remission or partial
remission after at least 8 weeks of prednisone at a dose of at least 60 mg.
- Patients who have compelling contraindications to the use of glucocorticoids,
such as morbid obesity, defined as BMI > 35 or diabetes mellitus
- Patients with idiopathic FSGS or collapsing glomerulopathy
Inclusion criteria for minors (between ages 4 and 18 years)
- Estimated average protein to creatinine ratio > 2.0 g/g despite use of an ACE
inhibitor or ARB. At least one-first void urine will be obtained and must have a
urine protein/creatinine ratio > 2.0 g/g to exclude the diagnosis of
orthostatic proteinuria
- Girls who are going through puberty and/or have menstrual periods must use
reliable birth control method to avoid pregnancy while participating in the
study
- Failed to respond with a complete remission or partial remission after at least
8 weeks of prednisone at a dose of at least 1 mg/kg
- Compelling contraindications to the use of glucocorticoids, such as morbid
obesity, defined as 99th percentile for age and sex or diabetes mellitus
- Patients with idiopathic FSGS or collapsing glomerulopathy
EXCLUSION CRITERIA:
- Age < 4 years.
- Prior intolerance of rituximab or other monoclonal antibody therapy, including
severe infusion reaction or hypersensitivity to murine proteins
- History of cardiac arrhythmias, unless cardiology consult approves the use of
rituximab.
- Prior total lifetime rituximab dose exceeding 1500 mg/m(2).
- Prior intolerance of cyclosporine.
- Severely impaired GFR, defined as Schwartz and MDRD eGFR < 50 ml/min/1.73m2.
-The rationale is that immunologic therapy is less likely to provide a clinical
benefit in the presence of advanced renal fibrosis.
- Patients with post-adaptive FSGS (including obesity-associated FSGS, reflux
nephropathy, reduced nephron mass). There is not a strong rationale for the use
of immunologic therapy in this population.
- Patients with genetic FSGS due to a high penetrance mutation, e.g. NPHS2
mutation. There is not a strong rational for the use of immunologic therapy in
this population.
- Medication-associated FSGS.
- Recurrent FSGS following renal transplant
- Chronic viral infection, such as HIV-1, hepatitis B, and hepatitis C. The
safety of aggressive immunologic therapy in these diseases is in question.
- Chronic bacterial infection. At baseline, if the patient gives a history of BCG
vaccination or prior positive PPD, we will consult with an infectious disease
clinician before enrolling the patient.
- Active malignancy
- Poorly controlled hypertension, defined as home BP measurements > 140/90 or
controlled blood pressure requiring 4 or more medications. The rationale is
that blood pressure elevation is common on cyclosporine therapy.
- Women and girls who are pregnant or trying to become pregnant or are unwilling
to practice birth control. Rituximab is in pregnancy class C: no systematic
evidence of safety. In humans, cyclosporine crosses the placenta. Cyclosporine
lacks genotoxic effects in human and animal studies. However, growth restriction
and prematurity occur in up to 40% of neonates born to mothers with organ
transplants who are treated with cyclosporine, but no congenital abnormalities
have been documented.
- Women and girls who are breastfeeding (possible immune suppression in infants as
well as the unknown effects on growth or association with carcinogenesis.)
- Predicted requirement for live vaccines over the 24 months following enrollment. |
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| Study is available at: |
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National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, MD 20892
United States
Primary Contact:
Patient Recruitment and Public Liaison Office
Email: prpl@mail.cc.nih.gov
Phone: (800) 411-1222 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 15, 2010 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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Clinical trials are medical research studies designed to test the safety and/or
effectiveness of new drugs, devices, or treatments in humans. These studies are
conducted worldwide for a range of conditions and illnesses. Learn more about
clinical research and participating in a study at
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