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Pilot Studies of Novel Therapies to Treat Resistant Focal Segmental Glomerulosclerosis (FSGS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00193648
Recruitment Status : Completed
First Posted : September 19, 2005
Last Update Posted : October 22, 2007
University of North Carolina
The Cleveland Clinic
Information provided by:
Northwell Health

Brief Summary:

The current management of primary FSGS is predicated on the assumption that the disease is caused by an immune-mediated disturbance in glomerular barrier function. Therefore, most treatment protocols have involved immunosuppressive drugs given singly or in combination. However, the efficacy of this type of therapy has been disappointing and the long-term prognosis for renal survival in patients with resistant FSGS is poor. An alternative approach that targets the fibrosis pathway may represent a novel approach to the treatment of resistant FSGS. In this R21, the investigators will test the hypothesis that two novel agents - a tumor necrosis factor-alpha (TNF-α) antagonist and a peroxisome proliferator activator receptor-gamma (PPARγ) agonist - can be administered safely to patients with resistant FSGS. In the R21 feasibility/pilot phase, pharmacokinetic studies will be conducted to assess the impact of proteinuria on the kinetics of the novel drugs in children and adults.

Specific Aim #1: To assess the safety and tolerability of two novel drugs - a TNF-α antagonist and a PPARγ agonist - in patients with resistant FSGS.

Specific Aim #2: To conduct a pharmacokinetic (PK) assessment of the selected agents to enable selection of medication regimens for investigation in a randomized Phase II study.

Condition or disease Intervention/treatment Phase
Focal Glomerulosclerosis Drug: Rosiglitazone (Avandia) Drug: Adalimumab (Humira) Phase 1

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Study Type : Interventional
Actual Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Novel Therapies for Resistant FSGS
Study Start Date : July 2005
Actual Study Completion Date : October 2007

Arm Intervention/treatment
Active Comparator: 1
Avandia (rosiglitazone)
Drug: Rosiglitazone (Avandia)
oral drug administration

Active Comparator: 2
Humira (adalimumab)
Drug: Adalimumab (Humira)
Injection of drug biweekly

Primary Outcome Measures :
  1. Safety and tolerance of medications [ Time Frame: 16 week treatment period ]

Secondary Outcome Measures :
  1. Reduction in proteinuria [ Time Frame: 16 week treatment period ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   2 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Aged 2-42 years at onset of proteinuria
  2. Aged ≤ 42 years at time of randomization (randomization date before 43rd birthday)
  3. Estimated glomerular filtration rate (GFR) ≥ 40 ml/min/1.73 m2 at most recent measurement prior to randomization

    1. For patients < age 18 years: Schwartz formula
    2. For patients ≥ age 18 years: Cockroft-Gault formula
  4. Up/c > 1.0 g/g creatinine on first morning void at time of randomization
  5. Biopsy confirmed as primary FSGS (including all subtypes) by study pathologist.
  6. Steroid resistance: During the last treatment course with high dose steroids prior to randomization, the patient must have demonstrated steroid resistance defined below and not have had a complete remission of proteinuria (Up/c < 0.2 or dipstick urine protein negative/trace) subsequently. The course of steroid treatment that defines resistance must be the same or equivalent to at least 4 weeks of every day dosing with a minimum cumulative dose of 56 mg/kg or 1680 mg of prednisone or its equivalent.
  7. May be taking angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocking agent (ARB), vitamin E, or lipid lowering therapy
  8. Willingness to comply with clinical trial protocol, medications, and follow-up visits, etc.
  9. Screen failure in FSGS-CT based on prior treatment with excluded medication
  10. Treatment failure in FSGS-CT based on failure to achieve remission after 26 weeks or 52 weeks of test therapy, i.e., cyclosporine or mycophenolate mofetil (MMF) + oral dexamethasone pulses

Exclusion Criteria

  1. Secondary FSGS
  2. Treated with cyclophosphamide, chlorambucil, levamisole, methotrexate, nitrogen mustard, or other immunosuppressive medications in the 30 days prior to randomization
  3. Lactation, pregnancy, or refusal of birth control in women of child bearing potential
  4. Participation in another therapeutic trial concurrently or for 30 days prior to randomization
  5. Active/serious infection (including, but not limited to hepatitis B or C, HIV)
  6. Malignancy
  7. Systemic lupus erythematosus (SLE) or multiple sclerosis
  8. Hepatic disease defined as serum AST/ALT > 2.5X the upper limit of normal
  9. Patients with blood pressure > 140/95 or > 95th percentile for age/height while receiving maximal doses of 3 or more antihypertensive agents.
  10. Diabetes mellitus (DM) type I or II.
  11. Hematocrit < 30%
  12. Organ transplantation
  13. Obesity (based on estimated dry weight at disease onset prior to steroid therapy) defined as:

    1. Body mass index (BMI) > 97th percentile for age if aged 2-20 years
    2. BMI > 40 kg/m2 if aged ≥ 21 years
  14. Allergy to study medications
  15. Inability to consent/assent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00193648

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United States, New York
Howard Trachtman
New Hyde Park, New York, United States, 11040
United States, North Carolina
Debbie Gipson
Chapel Hill, North Carolina, United States, 27599-7155
Sponsors and Collaborators
Northwell Health
University of North Carolina
The Cleveland Clinic
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Principal Investigator: Howard Trachtman, MD Schneider Children's Hospital of North Shore-LIJ Health System
Principal Investigator: Debbie Gipson, MD University of North Carolina
Principal Investigator: Tom Greene, PhD The Cleveland Clinic
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00193648    
Other Study ID Numbers: DK70341
First Posted: September 19, 2005    Key Record Dates
Last Update Posted: October 22, 2007
Last Verified: October 2007
Keywords provided by Northwell Health:
PPAR-gamma agonist
TNF-alpha antagonist
Steroid and immunosuppressive drug resistance
Resistant primary FSGS
Additional relevant MeSH terms:
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Glomerulosclerosis, Focal Segmental
Kidney Diseases
Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases
Tumor Necrosis Factor Inhibitors
Anti-Inflammatory Agents
Antirheumatic Agents
Hypoglycemic Agents
Physiological Effects of Drugs