Once-A-Month Steroid Treatment for Patients With Focal Segmental Glomerulosclerosis
This study will test the safety and effectiveness of a monthly dosing regimen of dexamethasone-a strong steroid medication-to treat patients with focal segmental glomerulosclerosis (FSGS). Patients with this disease have kidney fibrosis (scarring) and proteinuria (excessive excretion of protein in the urine) that, in about half of the patients eventually requires kidney dialysis or transplant. Currently, the most effective treatment for FSGS is high-dose steroids (prednisone) taken daily for 4 to 6 months. However, only about 30 percent of patients respond to this treatment, and it causes serious side effects in many patients. Other drugs, such as cyclosporin and cyclophosphamide, improve proteinuria in even fewer patients (about 10 percent) and also have serious side effects. This study will explore whether a monthly pulse dose of steroids will achieve disease remission with less toxicity.
Adults and children with FSGS who: 1) have not received steroid treatment, or 2) could not tolerate daily steroid treatment, or 3) relapsed after conventional steroid treatment may be eligible for this study. Those enrolled will take dexamethasone by mouth for 4 days every 4 weeks for a total of 8 months. Patients will undergo various tests before treatment starts (baseline), during the course of treatment, and in follow-up visits to evaluate the effects of treatment as follows:
- Review of kidney biopsy, medical evaluation, measurement of total daily urine protein excretion and kidney function, psychiatric testing for depression or other mood disorder
- Measurements of blood pressure, blood chemistries and urine protein excretion - monthly during treatment
- Questionnaire about the effects of treatment, if any, on mood and feelings - monthly during treatment
- Photographs of the face and body (in underwear or shorts and tank top) to evaluate body fat distribution- baseline and 8 months
- Eye examinations for cataracts and glaucoma - baseline and 8 months
- Bone density scan (DEXA scan) of the lower spine and hip - baseline, 4 and 12 months
- Magnetic resonance imaging (MRI) of the hips
- Psychological evaluation and quality of life evaluation - baseline, 1, 2 and 8 months
- Blood tests for adrenal gland function - baseline, 4 and 8 months
- Blood and urine tests - 10, 12, 15, and 18 months
Patients who achieve remission (whose urine protein levels decrease to normal) before completing the 8 months of dexamethasone will take one more dose and then stop therapy, but continue with follow-up. Patients who achieve remission but relapse may be offered a second course of treatment.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
|Official Title:||Pulse Dexamethasone in Focal Segmental Glomerulosclerosis|
|Study Start Date:||March 2000|
|Estimated Study Completion Date:||December 2004|
The objective of this study is to evaluate the effectiveness and toxicity of an alternative steroid dosing regimen for patients with focal segmental glomerulosclerosis (FSGS), using a pilot study design that will enroll 20 patients. Although the literature reports variable steroid responsiveness, remission rates of up to 30-40 percent have recently been reported in nephrotic adult patients treated with daily prednisone at 1 mg/kg/day for at least 4 months, followed by a taper over 3-4 months. Such a prolonged and aggressive steroid course is fraught with significant morbidity, but this approach has been advocated by some authors because of the poor prognosis for renal survival in nephrotic patients with FSGS who do not achieve remission with steroid treatment. We plan to test an eight month course of high dose steroid therapy administered in monthly pulses instead of daily doses, for comparable efficacy in achieving remission, and for the occurrence of adverse steroid side effects. We plan to enroll patients with nephrotic syndrome due to biopsy-proven FSGS, who have either not been treated, or have responded to conventional steroid dosing regimens and relapsed. We plan to treat them with monthly oral pulses of dexamethasone (40-60 mg/d x 4 days), for 8 months. The primary endpoint will be induction of complete remission, defined as urine protein less than 300 mg/d. Patients will also be evaluated for manifestations of steroid toxicity. Patients will be seen in follow up at intervals up to 24 months following study entry. If this study suggests that remission of nephrotic syndrome can be attained with this regimen, and with an acceptable toxicity profile, we will plan a randomized controlled trial of this regimen compared with daily or alternate day oral steroids.
|United States, Maryland|
|National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|
|Bethesda, Maryland, United States, 20892|