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Sponsored by: |
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
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Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00065611 |
Focal segmental glomerulosclerosis (FSGS) and minimal change disease are kidney diseases that are associated with increased excretion of protein in the urine. Approximately half of FSGS patients will lose kidney function within 8 years of diagnosis and will require dialysis. The purpose of this study is to determine whether intermittent oral steroid therapy can cause sustained remission of FSGS and MCD.
Approximately 70 participants, including adults and children older than age 2, will be enrolled in this study. They will receive 48 doses of oral dexamethasone over a period of 48 weeks. One group will take two daily doses every 2 weeks; the other group will take four daily doses every 4 weeks. Doctors will monitor participants before, during, and after the steroid treatment with extensive exams and testing. At the completion of the study, researchers will evaluate the safety and efficacy of the drug treatment.
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Condition | Intervention | Phase |
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Nephrosis Focal Lipoid Glomerulosclerosis |
Drug: Oral dexamethasone |
Phase III |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study |
Official Title: | Pulse Dexamethasone Over 48 Weeks for Podocyte Disease |
Estimated Enrollment: | 70 |
Study Start Date: | July 2003 |
The major causes of primary nephritic syndrome in adults and children are idiopathic podocyte diseases, minimal change (MCD) and focal segmental glomerulosclerosis (FSGS). Our objective is to determine whether intermittent oral dexamethasone administered over 48 weeks can induce complete remission in these patients. This is an open-label multi-center pilot study designed to obtain preliminary evidence of efficacy and to establish safety. This is part of a long-term effort to define the most effective mode of administering pulse dexamethasone and is expected to lead to a trial comparing daily prednisone to pulse dexamethasone.
We will enroll up to 70 patients with nephritic-level proteinuria due to biopsy-proven MCD (up to 30 patients) or FSGS (up to 40 patients). We will include adults and children greater than 2.0 years of age. Children with MCD must have received a minimum of 4 weeks and a maximum of 10 weeks of high-dose daily steroids, since many children are responsive to short courses of daily steroids; these requirements will define a steroid-resistant population. For children with FSGS and adults with MCD or FSGS, there is no minimum duration of prior steroids and there is a maximum of 8 weeks of prior high-dose daily steroids; these requirements will define a population that has received a short steroid course without response. If steroids have been used, inclusion criteria require persistent nephrotic syndrome (thus excluding steroid-sensitive nephrotic syndrome, whether steroid-dependent or frequently relapsing).
Patients may enroll at NIH or at collaborating centers. Those patients who enroll at NIH will visit the NIH Clinical Center at least 4 times. Patients enrolled at collaborating centers have the option to come to the NIH Clinical Center to complete research tests; under these circumstances they will be enrolled as NIH research subjects.
Patients will receive 48 doses of oral dexamethasone over a period of 48 weeks. Patients will be randomized to one of two arms: 2 daily doses every 2 weeks or 4 daily doses every 4 weeks. The rationale is to test whether increased frequency dosing has greater efficacy with acceptable safety. For adult patients, we have a record of safety with pulse dexamethasone from the FSGS Dexamethasone study as well as from published studies for other diseases. Therefore, for adults each pulse will be 50 mg/m(2) during the first 12 weeks and each pulse will be 25 mg/m(2) during the next 36 weeks. The trial for pediatric patients involves dose escalation, as there is little experience with pulse dexamethasone for podocyte diseases in this age group. In pediatric stage 1, each dexamethasone pulse will be 25 mg/m(2) over 48 weeks. When 4 patients in each arm have completed 48 weeks of therapy, safety and efficacy will be evaluated. If the evaluation is positive, we will embark on pediatric stage 2, in which dexamethasone pulses will be 50 mg/m(2) during the first 12 weeks and 25 mg/m(2) during the next 36 weeks (the same as the adult regimen).
The primary endpoint will be the presence of complete remission 48 weeks after beginning therapy. Secondary endpoints will include complete and partial remission at 48 weeks, and complete and partial remission at 104 weeks. Assessment of remission will be by 24 hour urine collection in adults and children greater than 13.0 years and first void urine samples in children less than 13.0 years. Patients will be evaluated for manifestations of steroid toxicity, including growth rate (children), ophthalmologic complications, adrenal suppression, osteoporosis, a vascular necrosis, and psychological disturbances.
Ages Eligible for Study: | 2 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
INCLUSION CRITERIA:
Diagnosis:
A) Biopsy-proven MCD and its variants, including IgM nephropathy and MCD with mesangial hypertrophy.
B) Biopsy-proven FSGS, including idiopathic FSGS and collapsing FSGS. We will exclude patients with HIV-associated FSGS, as the risks of steroids are increased in these patients. We will exclude hyperfiltration FSGS associated with morbid obesity (BMI greater than 40 kg/m(2)), sickle cell anemia, reflux nephropathy, chronic tubular injury, congenital renal anomalies, and reduced nephron mass; the rationale is that these FSGS variants are considered refractory to steroids.
Prior immunosuppressive therapy:
For children with MCD, we require a minimum of 4 weeks and a maximum of 10 weeks of daily steroid therapy at a dose of greater than or equal to 60 mg/m(2) with proteinuria persisting in the nephrotic range (excluding steroid-sensitive, steroid-dependent and frequently relapsing MDC).
For children with FSGS and adults with MCD and FSGS, we require no minimum and a maximum of 8 weeks of daily or alternate day steroids at a dose of greater than 0.5 mg/kg with proteinuria persisting in the nephrotic range.
Patients with prior immunosuppressive therapy other than steroids are eligible.
EXCLUSION CRITERIA:
Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
Contact: TTY | 1-866-411-1010 |
United States, Maryland | |
National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
Bethesda, Maryland, United States, 20892 | |
United States, Minnesota | |
Mayo Clinic, Rochester | Recruiting |
Rochester, Minnesota, United States, 55905 |
Responsible Party: | National Institutes of Health ( Jeffrey B. Kopp, M.D./National Institute of Diabetes and Digestive and Kidney Diseases ) |
Study ID Numbers: | 030226, 03-DK-0226 |
Study First Received: | July 28, 2003 |
Last Updated: | January 16, 2009 |
ClinicalTrials.gov Identifier: | NCT00065611 |
Health Authority: | United States: Federal Government |
Steroids Osteoporosis Proteinuria Minimal Change Disease Focal Segmental Glomerulosclerosis |
Focal Segmental Glomerulosclerosis FSGS Minimal Change Disease MCD Kidney Disease |
Dexamethasone Glomerulosclerosis, Focal Segmental Nephrosis Proteinuria Nephrosis, Lipoid |
Urologic Diseases Osteoporosis Kidney Diseases Dexamethasone acetate Focal segmental glomerulosclerosis |
Anti-Inflammatory Agents Antineoplastic Agents, Hormonal Antineoplastic Agents Physiological Effects of Drugs Gastrointestinal Agents Hormones, Hormone Substitutes, and Hormone Antagonists Antiemetics |
Glucocorticoids Hormones Pharmacologic Actions Autonomic Agents Therapeutic Uses Peripheral Nervous System Agents Central Nervous System Agents |