Clinical trial NCT00065611
Conditions: Nephrosis Focal Lipoid Glomerulosclerosis
Keywords: Steroids Osteoporosis Proteinuria Minimal Change Disease Focal Segmental Glomerulosclerosis FSGS MCD Kidney Disease
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Start date: 2003-07-01; Completion date: 2010-08-01
Enrollment: 8 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:
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.

Interventions: intervention 1: Oral dexamethasone
Intervention descriptions: intervention 1: Stage I: Dexamethasone 25 mg/m2, 2 doses every 2 weeks over 48 weeks or dexamethasone 25 mg/m2, 4 doses every 4 weeks over 48 weeks.

Stage II: 1.) Dexamethasone 50 mg/m2, 2 daily doses every 12 weeks, followed by 25 mg/m2, 2 daily doses every 2 weeks over 36 weeks, or 2.) Dexamethasone 50 mg/m2, 4 daily doses every 4 weeks over 12 weeks, followed by 25 mg/m2, 4 daily doses every 4 weeks over 36 weeks.

over 36 weeks.

Protocol documents: