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Focal Segmental Glomerulosclerosis Clinical Trial (FSGS-CT)

This study has been completed.
Sponsor:
Collaborator:
The Cleveland Clinic
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00135811
First received: August 24, 2005
Last updated: May 21, 2012
Last verified: May 2012
  Purpose

The FSGS Clinical Trial is a multi-center, prospective, controlled, open label randomized trial designed to determine if treatment with mycophenolate mofetil (MMF) in conjunction with pulse steroids is superior to treatment with Cyclosporine-A (CSA) in inducing remission from proteinuria over 12 months.


Condition Intervention Phase
Glomerulosclerosis, Focal
Drug: Cyclosporin
Drug: MMF and Dexamethasone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Focal Segmental Glomerulosclerosis Clinical Trial

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • The primary outcome is a 6-level ordinal variable defined based on the achievement of remission from proteinuria during the first 52 weeks after randomization. [ Time Frame: first 52 weeks after randomization. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The main secondary outcome is a 5-level ordinal variable defined based on the persistence of remissions after immunosuppressive agents are withdrawn. [ Time Frame: based on the participant's level of proteinuria during the period from week 52 through week 78 following withdrawal of CSA or MMF/Pulse steroids ] [ Designated as safety issue: No ]

Estimated Enrollment: 207
Study Start Date: November 2004
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Cyclosporin
Drug: Cyclosporin
Participants assigned to this group will initiate treatment with CSA, 5-6 mg/kg per day with a 250 mg/day maximum starting dose, divided into two daily doses. The CSA dose will be adjusted based on drug levels determined at specified study visits in order to achieve a 12-hour trough concentration in the therapeutic range of 100-250 ng/ml.
Active Comparator: 2
MMF and Dexamethasone
Drug: MMF and Dexamethasone

MMF, 25-36 mg/kg per day with a maximum dose of 2 g/day divided into two daily doses. The dose range reflects the use of fixed size (250 mg) capsules and application of defined daily doses to specific weight ranges (see Table below). In younger children or those participants who are unable to swallow capsules, a liquid formulation will be used to provide 36 mg/kg per day to a maximum of 2 g per day. The starting MMF dose will be 0.5-0.67 of the full dose for 2 weeks before advancing to the full dose for the duration of the 12-month treatment period.

Dexamethasone, 0.9 mg/kg per dose, with a maximum dose of 40 mg


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   2 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 2-40 years at onset of signs or symptoms of FSGS
  • Age ≤ 40 years at time of randomization (randomization date before 41st birthday)
  • Estimated GFR ≥ 40 ml/min/1.73 m2 at most recent measure prior to randomization

    • For participants < age 18 years: Schwartz formula
    • For participants ≥ age 18 years: Cockroft-Gault formula
  • Up/c > 1.0 g protein/g creatinine on first am void at time of randomization
  • Biopsy confirmed as primary FSGS (including all subtypes) by study pathologist. A minimum of 1 glomerulus demonstrating segmental sclerosis on light microscopy will be required to confirm the diagnosis.
  • Steroid resistance: The participant must have demonstrated steroid resistance (defined as a failure to achieve a sustained Up/c ≤ 1.0) based on at least one treatment course with high dose steroids prior to randomization which satisfies both of the following conditions:

    • minimal treatment duration of 4 weeks
    • minimum cumulative dose of 56 mg/kg or 1680 mg of prednisone or its equivalent. In addition, the participant must not have had a complete remission of proteinuria (Up/c < 0.2 or dipstick urine protein 0/trace) subsequent to the latest qualifying 4-week course demonstrating steroid resistance.
  • Willingness to follow the clinical trial protocol, including medications, and baseline and follow-up visits and procedures.
  • Participants may be taking ACEI, ARB, Vitamin E, or lipid lowering therapy.

Exclusion Criteria:

  • Secondary FSGS
  • Prior therapy with sirolimus, CSA, tacrolimus, MMF, or azathioprin (Imuran)
  • Treated with cytoxan, chlorambucil, levamisole, methotrexate, or nitrogen mustard in the last 30 days
  • Lactation, pregnancy, or refusal of birth control in women of child bearing potential
  • Participation in another therapeutic trial concurrently or 30 days prior to randomization
  • Active/serious infection (including, but not limited to Hepatitis B, C, or HIV)
  • Malignancy
  • Blood pressure > 140/95 or > 95th percentile for age/height.
  • Participant is receiving 4 or more antihypertensive agents for the primary purpose of controlling blood pressure.
  • Participants with previously diagnosed diabetes mellitus type I or II: the diagnosis of DM I or II will be based on local criteria for participants with an established diagnosis. If hyperglycemia is detected during the screening period, the WHO criteria for the diagnosis of DM I and II will be used.
  • Clinical evidence of cirrhosis or chronic active liver disease
  • Abnormal laboratory values at the time of study entry:

    • Absolute neutrophil count (ANC) < 2000/mm3, or
    • Hematocrit (HCT) < 28%
  • History of significant gastrointestinal disorder, e.g, severe chronic diarrhea (> 5 watery stools per day) or active peptic ulcer disease.
  • Organ transplantation
  • Obesity (based on estimated dry weight at onset of disease prior to steroid therapy) defined as

    • BMI > 97th percentile for age if aged 2-20 years
    • BMI > 40 kg/m2 for age ≥21 years
  • Allergy to study medications
  • Inability to consent/assent

Note: Participants with conditions meeting exclusion criteria at a particular evaluation for eligibility may be re-evaluated at a later time to determine if the conditions have changed so that all entry criteria are met. In particular, if blood pressure > 140/95 or > 95th percentile for age/height while the participant is on less than three antihypertensive agents, the participant may be re-evaluated for eligibility after adding other antihypertensive agents so long as the total number of agents does not exceed three.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00135811

Locations
United States, Ohio
Data Coordinating Center; Cleveland Clinic Foundation; Quantitative Health Sciences; 9500 Euclid Avenue
Cleveland, Ohio, United States, 44195-5196
Sponsors and Collaborators
The Cleveland Clinic
Investigators
Study Chair: Aaron Friedman, MD University of Minnesota - Clinical and Translational Science Institute
Study Director: Marva Moxey-Mims, MD, FAAP National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Additional Information:
No publications provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Marva Moxey-Mims, M.D., NIH Project Officer
ClinicalTrials.gov Identifier: NCT00135811     History of Changes
Other Study ID Numbers: 63490 (completed)
Study First Received: August 24, 2005
Last Updated: May 21, 2012
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Focal Segmental Glomerulosclerosis

Additional relevant MeSH terms:
Glomerulosclerosis, Focal Segmental
Glomerulonephritis
Kidney Diseases
Nephritis
Urologic Diseases
BB 1101
Cyclosporine
Cyclosporins
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Autonomic Agents
Central Nervous System Agents
Dermatologic Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on November 20, 2014