NCT00193648

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
21

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jul 2005

Typical duration for phase_1

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2005

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

September 10, 2005

Completed
9 days until next milestone

First Posted

Study publicly available on registry

September 19, 2005

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2007

Completed
Last Updated

October 22, 2007

Status Verified

October 1, 2007

First QC Date

September 10, 2005

Last Update Submit

October 19, 2007

Conditions

Focal Glomerulosclerosis

Keywords

FSGSPharmacokineticsRosiglitazonePPAR-gamma agonistAdalimumabTNF-alpha antagonistSteroid and immunosuppressive drug resistanceResistant primary FSGS

Outcome Measures

Primary Outcomes (1)

  • Safety and tolerance of medications

    16 week treatment period

Secondary Outcomes (1)

  • Reduction in proteinuria

    16 week treatment period

Study Arms (2)

1

ACTIVE COMPARATOR

Avandia (rosiglitazone)

Drug: Rosiglitazone (Avandia)

2

ACTIVE COMPARATOR

Humira (adalimumab)

Drug: Adalimumab (Humira)

Interventions

Rosiglitazone (Avandia)DRUG

oral drug administration

1
Adalimumab (Humira)DRUG

Injection of drug biweekly

2

Eligibility Criteria

Age2 Years - 40 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Aged 2-42 years at onset of proteinuria
  • Aged ≤ 42 years at time of randomization (randomization date before 43rd birthday)
  • Estimated glomerular filtration rate (GFR) ≥ 40 ml/min/1.73 m2 at most recent measurement prior to randomization
  • For patients \< age 18 years: Schwartz formula
  • For patients ≥ age 18 years: Cockroft-Gault formula
  • Up/c \> 1.0 g/g creatinine on first morning void at time of randomization
  • Biopsy confirmed as primary FSGS (including all subtypes) by study pathologist.
  • 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.
  • May be taking angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocking agent (ARB), vitamin E, or lipid lowering therapy
  • Willingness to comply with clinical trial protocol, medications, and follow-up visits, etc.
  • Screen failure in FSGS-CT based on prior treatment with excluded medication
  • 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

You may not qualify if:

  • Secondary FSGS
  • Treated with cyclophosphamide, chlorambucil, levamisole, methotrexate, nitrogen mustard, or other immunosuppressive medications in the 30 days prior to randomization
  • Lactation, pregnancy, or refusal of birth control in women of child bearing potential
  • Participation in another therapeutic trial concurrently or for 30 days prior to randomization
  • Active/serious infection (including, but not limited to hepatitis B or C, HIV)
  • Malignancy
  • Systemic lupus erythematosus (SLE) or multiple sclerosis
  • Hepatic disease defined as serum AST/ALT \> 2.5X the upper limit of normal
  • Patients with blood pressure \> 140/95 or \> 95th percentile for age/height while receiving maximal doses of 3 or more antihypertensive agents.
  • Diabetes mellitus (DM) type I or II.
  • Hematocrit \< 30%
  • Organ transplantation
  • Obesity (based on estimated dry weight at disease onset prior to steroid therapy) defined as:
  • Body mass index (BMI) \> 97th percentile for age if aged 2-20 years
  • BMI \> 40 kg/m2 if aged ≥ 21 years
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Howard Trachtman

New Hyde Park, New York, 11040, United States

Location

Debbie Gipson

Chapel Hill, North Carolina, 27599-7155, United States

Location

Related Publications (2)

  • Liu ID, Willis NS, Craig JC, Hodson EM. Interventions for idiopathic steroid-resistant nephrotic syndrome in children. Cochrane Database Syst Rev. 2025 May 8;5(5):CD003594. doi: 10.1002/14651858.CD003594.pub7.

    PMID: 40337980DERIVED

  • 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: 35224732DERIVED

MeSH Terms

Conditions

Glomerulosclerosis, Focal Segmental

Interventions

RosiglitazoneAdalimumab

Condition Hierarchy (Ancestors)

GlomerulonephritisNephritisKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

ThiazolidinedionesThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • 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

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

September 10, 2005

First Posted

September 19, 2005

Study Start

July 1, 2005

Study Completion

October 1, 2007

Last Updated

October 22, 2007

Record last verified: 2007-10

Locations

US(2)