Steroid Treatment for Kidney Disease

NCT00065611 | Completed Phase 3 Results

• 2 other identifiers: 03022603-DK-0226
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Nephrosis; Focal Lipoid Glomerulosclerosis

Keywords

Steroids; Osteoporosis; Proteinuria; Minimal Change Disease; Focal Segmental Glomerulosclerosis; FSGS; MCD; Kidney Disease

Outcome Measures

Primary Outcomes (1)

• Remission Status of Patients After Intermittent Oral Dexamethasone Administered Over 48 Weeks

  Complete remission is defined as proteinuria \<0.3 g/d. Partial remission is defined as a 50% fall in proteinuria compared to baseline, proteinuria \<3.5 g/d, and a preserved estimated glomerular filtration rate (eGFR), specified as \>60% of baseline. Limited response is defined as a 50% fall in proteinuria compared to baseline. All other outcomes are described as non-response.

  48 weeks from baseline

Secondary Outcomes (2)

• Urine Protein

  48 weeks from baseline

• CKD-EPI eGFR

  48 weeks from baseline

Interventions

Oral dexamethasone DRUG

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.

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults and children greater than 2.0 years of age are eligible. We will exclude children less than 2.0 years of age in light of the higher risk of steroid therapy in this age group and the higher likelihood genetic or syndromic FSGS, which is less likely to respond to steroids.
• 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.
• Proteinuria: patients must have nephrotic range proteinuria. Baseline tests will be obtained when patients have been off all immunosuppressive therapy for greater than or equal to 1 month.
• Renal function: estimated GFR must be greater than or equal to 40 ml/min/1.73m(2) at the time of study entry; In children weighing less than 40kg, GFR will be estimated by the Schwartz formula and expressed as GFR/1.73m(2): GFR equal to \[0.7 (males) or 0.57 (females) X height (cm)\]/ serum creatinine.
• Angiotensin antagonists: Patients must be receiving angiotensin antagonist therapy, at any dose approved by the FDA. Nephrotic range proteinuria will be defined as urine protein greater than or equal to 3.5 g/1.73m(2)/d (adults) and greater than 50 mg/kg (children less than 40 kg) while receiving maximally tolerated dose of angiotensin antagonist therapy for at least 4 weeks prior to study entry.
• 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.
• If hypertensive, adequate blood pressure control (target BP less than 125/75 mm Hg at greater than 75% of measurements in adults).
• Women with reproductive potential who are sexually active must maintain an effective birth control regimen (oral contraceptive, intrauterine device, or barrier method plus spermicide) and must have a negative urine HCG test prior to beginning therapy.
• Patients must either have a negative PPD test within 3 months of study entry while off immunosuppressive therapy or, if they have a history of positive PPD, they must have appropriate evaluation to exclude untreated tuberculosis (with the advice of an Infectious Disease consultant).

You may not qualify if:

• Patients with diabetes mellitus type 1 will be excluded, as these patients typically have brittle diabetic control that increases the risk of steroid treatment. Patients with diabetes mellitus type 2 will be included they manifest good glycemic control (glycosylated hemoglobin less than 7.5%), if they have lack proliferative retinopathy (the presence of proliferative retinopathy would place them at high risk for vision loss if steroids worsened glycemic control) and if they have had a renal biopsy within 6 months of study entry that shows no evidence for diabetic nephropathy.
• Poorly controlled hypertension (greater than 25% of values greater than 125/75).
• Immunosuppressive medication other than glucocorticoids, whether for podocyte disease or another indication, must have been discontinued greater than 8 weeks prior to study entry. This does not apply to topical immunosuppressant medication.
• Pregnancy.
• Existence of any other condition that would complicate the implementation or interpretation of the study.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Adhikari M, Bhimma R, Coovadia HM. Intensive pulse therapies for focal glomerulosclerosis in South African children. Pediatr Nephrol. 1997 Aug;11(4):423-8. doi: 10.1007/s004670050309.

  PMID: 9260238 BACKGROUND

• Yorgin PD, Krasher J, Al-Uzri AY. Pulse methylprednisolone treatment of idiopathic steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2001 Mar;16(3):245-50. doi: 10.1007/s004670000494.

  PMID: 11322372 BACKGROUND

• Houser MT, Jahn MF, Kobayashi A, Walburn J. Assessment of urinary protein excretion in the adolescent: effect of body position and exercise. J Pediatr. 1986 Sep;109(3):556-61. doi: 10.1016/s0022-3476(86)80143-3.

  PMID: 3746552 BACKGROUND

• Hodson EM, Sinha A, Cooper TE. Interventions for focal segmental glomerulosclerosis in adults. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD003233. doi: 10.1002/14651858.CD003233.pub3.

  PMID: 35224732 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Nephrosis; Osteoporosis; Proteinuria; Nephrosis, Lipoid; Glomerulosclerosis, Focal Segmental; Macular dystrophy, corneal type 1; Kidney Diseases

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Glomerulonephritis; Nephritis

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Jeffrey B Kopp, MD
• Organization: NIDDK, NIH

jbkopp@nih.gov

3015943403

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2003
• First Posted: July 29, 2003
• Study Start: July 1, 2003
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: October 28, 2011
• Results First Posted: October 28, 2011

Record last verified: 2011-09

Locations

US (1)