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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Novel Therapies for Resistant FSGS

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.


Detailed Summary:

Description of study visits

Screening Visit: Eligibility Studies

  1. History and physical examination
  2. Urine protein and creatinine excretion. Proteinuria (Up/c) will be expressed as the protein:creatinine ratio (mg:mg) in a single early morning specimen.
  3. Serum creatinine and calculated GFR. The GFR will be calculated using the Schwartz formula for patients below 18 years of age and Cockroft-Gault for those 18 years or older.
  4. Serum Na+, K+, HCO3-, Cl-, glucose, BUN, albumin, cholesterol, AST, ALT, alkaline phosphatase, CBC, ANA, CH50, pregnancy test
  5. HIV, Hepatitis B and C serology, if not done in the previous 12 months
  6. TB skin test, if not done in the previous 12 months
  7. Existing renal biopsy tissue will be assessed for all subjects who have not had the diagnosis of FSGS confirmed by an FSGS-CT core pathologist (only in screen failures).

Baseline Visit: Week 0 Visit

  1. Serum glucose, albumin, and creatinine concentrations
  2. TNF-alpha level
  3. Baseline anti-adalimumab antibody (AAA) level in patients assigned to Humira® treatment
  4. A urine, plasma, serum and DNA sample will be collected for storage in the NIDDK FONT Biorepositories at Fisher Bioservice and the Rutgers Cell & DNA Repository for patients who consent to this procedure. A request will be made to store any residual renal tissue collected for clinical indications during the FONT trial in the N
    Sponsor: Northwell Health

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

    Original Primary Outcome:

    • PK characteristics
    • Safety and tolerance of drugs


    Current Secondary Outcome: Reduction in proteinuria [ Time Frame: 16 week treatment period ]

    Original Secondary Outcome: Reduction in proteinuria

    Information By: Northwell Health

    Dates:
    Date Received: September 10, 2005
    Date Started: July 2005
    Date Completion:
    Last Updated: October 19, 2007
    Last Verified: October 2007