Permeability Factor in Focal Segmental Glomerulosclerosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )
ClinicalTrials.gov Identifier:
NCT00007475
First received: December 22, 2000
Last updated: February 8, 2016
Last verified: February 2016
Results First Received: June 19, 2015  
Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Focal Segmental Glomerulosclerosis
Interventions: Procedure: Plasma exchange
Drug: Cyclophosphamide

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Enrollment of subjects occurred at fraction of the anticipated rate despite over a decade of study conduct; the discrepancy between actual (15) and projected (100) enrollment is due to (a) lack of revising the registry entry with revisions of the protocol (n=50, excluding historical controls) and (b) lower referral rates by external nephrologists.

Reporting Groups
  Description
FPF NOT Assayed, Plasma Exchange + Cyclophosphamide Completed Participants not assayed for FSGS Permeability Factor (FPF) levels pre-treatment (Tx), yet still complete both series of protocol-specified treatment; FPF levels NOT available as its assay has not yet been developed to an extent that it could be applied to all enrollees of this current trial
FPF Assayed Pre-Tx as Low, PE + Cyclophosphamide Completed Protocol Groups A/B/C (FPF < 0.6); group size is limited due to limited availability of provisionally validated FPF assay and discrepancy with protocol groups due to low-FPF participants receiving PE and Cyclophosphamide (contrast to protocol Figure 1)
FPF Assayed Pre-Tx as High, PE + Cyclophosphamide Completed Protocol Group D (FPF 0.6 or greater pre-initial Transplant); group size is limited due to limited availability of provisionally validated FPF assay and discrepancy with protocol groups due to low-FPF participants receiving PE and Cyclophosphamide (contrast to protocol Figure 1)
Historical Controls Noted as Group F in study protocol: historical control patients, including patients at NIH or other institutions who have previously undergone renal transplant, for whom stored sera are available, and for whom consent to measure FPF has been can be obtained. In some cases, these measurements have been performed by Dr. Savin under pre-existing protocols and these data are already available.

Participant Flow:   Overall Study
    FPF NOT Assayed, Plasma Exchange + Cyclophosphamide Completed     FPF Assayed Pre-Tx as Low, PE + Cyclophosphamide Completed     FPF Assayed Pre-Tx as High, PE + Cyclophosphamide Completed     Historical Controls  
STARTED     12 [1]   1 [2]   2 [2]   0  
FSGS Permeability Factor (FPF) Assayed     0 [3]   1     2     0  
Initial Transplant     12     1     2     0  
Post-initial Transplant Proteinuria     12     1     2     0  
Initial Plasma Exchange     12     1     2     0  
Initiate Cyclophosphamide     12     1     2     0  
COMPLETED     8     1     2     0  
NOT COMPLETED     4     0     0     0  
Withdrawal by Subject                 1                 0                 0                 0  
Adverse Event                 3                 0                 0                 0  
[1] [ arm reflects un-assayed participants' disposition ]
[2] [ arm reflects eventual participant disposition ]
[3] FSGS Permeability Factor's provisional assay only applied to minority of early enrollees, by design.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
FPF NOT Assayed Provisionally, PE + Cyclophosphamide Completed Participants not provisionally assayed for FPF, yet still complete both series of protocol treatment: Plasma Exchange (PE) and Cyclophosphamide; note that these form a majority of enrollees due to limited availability of validated FPF assay (such an assay has not yet been developed to an extent that it could be applied to all enrollees of this current trial; see Outcome Measures for more details)
FPF Assayed Pre-Tx as Low, PE + Cyclophosphamide Completed Protocol Groups A/B/C (FPF < 0.6); group size is limited due to limited availability of validated FPF assay and discrepancy with protocol groups due to low-FPF participants receiving PE and Cyclophosphamide (contrast to protocol Figure 1)
FPF Assayed Pre-Tx as High, PE + Cyclophosphamide Completed Protocol Group D (FPF 0.6 or greater pre-initial Transplant); group size is limited due to limited availability of validated FPF assay
Total Total of all reporting groups

Baseline Measures
    FPF NOT Assayed Provisionally, PE + Cyclophosphamide Completed     FPF Assayed Pre-Tx as Low, PE + Cyclophosphamide Completed     FPF Assayed Pre-Tx as High, PE + Cyclophosphamide Completed     Total  
Number of Participants  
[units: participants]
  12     1     2     15  
Age  
[units: years at consent]
Median (Inter-Quartile Range)
  39.5   (32.25 to 47.25)     63   (63 to 63)     19   (18.5 to 19.5)     37   (25 to 48.5)  
Gender  
[units: participants]
       
Female     8     0     1     9  
Male     4     1     1     6  
Race (NIH/OMB)  
[units: participants]
       
American Indian or Alaska Native     0     0     0     0  
Asian     3     0     0     3  
Native Hawaiian or Other Pacific Islander     0     0     0     0  
Black or African American     3     0     0     3  
White     6     1     2     9  
More than one race     0     0     0     0  
Unknown or Not Reported     0     0     0     0  
Region of Enrollment  
[units: participants]
       
United States     12     1     2     15  
Treated for Prior Recurrence  
[units: participants]
       
Yes     2     1     0     3  
No     10     0     2     12  
Time from onset/diagnosis of Focal Segmental Glomerulosclerosis to study enrollment/consent [1]
[units: years]
Median (Inter-Quartile Range)
  10   (7.75 to 14.75)     6   (6 to 6)     1.5   (1.25 to 1.75)     8   (4 to 13.5)  
[1] Note: calculated in terms of whole years, subject to coarsening due to integer subtraction (whole-year age at consent - whole-year age at onset)



  Outcome Measures
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1.  Primary:   Reduction in Proteinuria in Recurrent FSGS Following Renal Transplant With Plasma Exchange and Cyclophosphamide.   [ Time Frame: every 3 months up to a year followed with native kidneys ]

2.  Secondary:   Comparison of RNA Expression Profiles in PBMC From Patients With FPF, Without FPF and Control Subjects   [ Time Frame: End of study ]

3.  Secondary:   Define the Kinetics of FPF in FSGS Patients Receiving Immunomodulatory Therapy or Plasma Exchange.   [ Time Frame: End of study ]

4.  Secondary:   Correlate the Effect of Immunosuppressive Agents Which Reduce Proteinuria in Recurrent FSGS With the Effect on FPF Levels   [ Time Frame: End of study ]

5.  Secondary:   Determine Whether Renal Transplantation in Patients Whose Elevated FPF Levels Have Been Reduced for a Sustained Period is Associated With a Reduced Prevalence of Recurrent FSGS.   [ Time Frame: End of study ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Note: definitive FSGS Permeability Factor (FPF) assays still in development. Data/samples transferred to the NIH-CC Glomerulosclerosis Consolidation protocol: focus on cardiotrophin like cytokine 1 & antibodies to a panel of podocyte proteins as FPF.


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Jeffrey B. Kopp, MD
Organization: National Institute of Diabetes & Digestive & Kidney Diseases
phone: +1 (301) 594-3403
e-mail: jbkopp@nih.gov


Publications:

Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )
ClinicalTrials.gov Identifier: NCT00007475     History of Changes
Other Study ID Numbers: 010053
01-DK-0053 ( Other Identifier: National Institutes of Health )
Study First Received: December 22, 2000
Results First Received: June 19, 2015
Last Updated: February 8, 2016
Health Authority: United States: Federal Government