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Catalytic Antibodies to Predict Uninvasively Late Transplant Failure (CATAPULT)

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.
 
ClinicalTrials.gov Identifier: NCT02843295
Recruitment Status : Completed
First Posted : July 25, 2016
Last Update Posted : August 25, 2016
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Tracking Information
First Submitted Date  ICMJE July 21, 2016
First Posted Date  ICMJE July 25, 2016
Last Update Posted Date August 25, 2016
Study Start Date  ICMJE September 2010
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 22, 2016)
  • PFR-MCA hydrolysis by circulating IgG (mmol/min/mol) [ Time Frame: at 3 months post-transplantation ]
  • PFR-MCA hydrolysis by circulating IgG (mmol/min/mol) [ Time Frame: at 6 months post-transplantation ]
  • PFR-MCA hydrolysis by circulating IgG (mmol/min/mol) [ Time Frame: at 9 months post-transplantation ]
  • PFR-MCA hydrolysis by circulating IgG (mmol/min/mol) [ Time Frame: at 12 months post-transplantation ]
  • PFR-MCA hydrolysis by circulating IgG (mmol/min/mol) [ Time Frame: at 18 months post-transplantation ]
  • PFR-MCA hydrolysis by circulating IgG (mmol/min/mol) [ Time Frame: at 24 months post-transplantation ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2016)
  • Glomerular filtration rate by MDRD formula (ml/min) [ Time Frame: at 3 months post-transplantation ]
  • Glomerular filtration rate by MDRD formula (ml/min) [ Time Frame: at 6 months post-transplantation ]
  • Glomerular filtration rate by MDRD formula (ml/min) [ Time Frame: at 9 months post-transplantation ]
  • Glomerular filtration rate by MDRD formula (ml/min) [ Time Frame: at 12 months post-transplantation ]
  • Glomerular filtration rate by MDRD formula (ml/min) [ Time Frame: at 18 months post-transplantation ]
  • Glomerular filtration rate by MDRD formula (ml/min) [ Time Frame: at 24 months post-transplantation ]
  • Proteinuria/creatinuria ratio (g/g) [ Time Frame: at 3 months post-transplantation ]
  • Proteinuria/creatinuria ratio (g/g) [ Time Frame: at 6 months post-transplantation ]
  • Proteinuria/creatinuria ratio (g/g) [ Time Frame: at 9 months post-transplantation ]
  • Proteinuria/creatinuria ratio (g/g) [ Time Frame: at 12 months post-transplantation ]
  • Proteinuria/creatinuria ratio (g/g) [ Time Frame: at 18 months post-transplantation ]
  • Proteinuria/creatinuria ratio (g/g) [ Time Frame: at 24 months post-transplantation ]
  • Interstitial fibrosis on graft biopsy (%) [ Time Frame: at day 0 ]
  • Interstitial fibrosis on graft biopsy (%) [ Time Frame: at 12 months post-transplantation ]
  • Interstitial fibrosis on graft biopsy (%) [ Time Frame: at 24 months post-transplantation ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Catalytic Antibodies to Predict Uninvasively Late Transplant Failure
Official Title  ICMJE Catalytic Antibodies to Predict Uninvasively Late Transplant Failure
Brief Summary Chronic Allograft Nephropathy (CAN), a major cause of late allograft failure, is characterized by a progressive decline in graft function correlating with tissue destruction. Recent data suggest that it may be possible to delay graft destruction if adequate management is initiated early (ie, at the stage of subclinical CAN). It is therefore essential to design new tests allowing physicians to predict transplant recipients prone to develop CAN
Detailed Description

Superantibodies are multifunctional antibodies combining the classical antigen-binding function with nonclassical biological activities, such as protease-like activity. In the past few years the role of proteolytic SuperAntibody (pSAb) has been evidenced in many biological processes in which their role may be either deleterious (autoimmune disease, alloimmune response against) or beneficial (sepsis).

Nothing is known so far regarding the role of pSAb in the setting of solid organ transplantation.

Preliminary data

The investigator has obtained preliminary results from a retrospective case control study indicating that an elevated serine protease activity of circulating IgG (measured by the hydrolysis of a synthetic fluorescent substrate: Proline-Phenylalanine-Arginine-Methylcoumarinamide (PFR-MCA)), correlates with the absence of CAN on protocol biopsy performed 2 years post-transplantation. Interestingly, low level of proteolysis IgG, measured 3 months post-transplantation, were also predictive of CAN at 2 years down the lane.

Aim of the Research project:

The aim is to validate in a prospective study, the potential of pSAb as predictive marker for CAN

100 recipients of a renal graft have to be enrolled and followed for 2 years.

The level of PFR-MCA hydrolysis by circulating Immunoglobulin G (IgG) will be measured before the transplantation and every 3 months up to one year and every 6 months thereafter until 2 year post-transplantation. The development of CAN will be assessed by estimated glomerular filtration rate (Modification of the Diet in Renal Disease (MDRD) formula), the proteinuria and the histological examination of the graft (screening biopsy at 3 months and 1 year will be analysed using a computerized color image analysis to quantify interstitial fibrosis).

The capacity of the pSAb test to predict CAN will be validated and the sensibility and specificity of this test will be calculated. The optimal cut-off value will be determined from the Receiver Operating Characteristic (ROC) analysis. The accuracy of the test will be evaluated in subgroups displaying various risk factors for CAN.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Condition  ICMJE Renal Transplantation
Intervention  ICMJE Other: blood samples
Study Arms  ICMJE Experimental: Population of the study
3 stratification groups: Group 1: High immunologic risk Patients receiving a ≥ 2nd graft and/or Panel Reactive Antibody ≥ 30% and/or Human Leukocyte Antigen (HLA) mismatches ≥ 4 Group 2: High non-immunologic risk Donors over 60 years of age and/or Donor between 50 to 59 years of age who have died of stroke, or had a history of high blood pressure, or at the time of death had a creatininemia ≥ 135 µmol/L Group 3: Low risk Patients not included in Groups 1 or 2
Intervention: Other: blood samples
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 22, 2016)
100
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2015
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age > 18 the day of transplantation
  • Recipient of a renal graft
  • Informed consent to participate to the study
  • Patient transplanted and followed 2 years in one of the 3 transplantation centers of the study (Hospital Edouard Herriot or Centre Hospitalier Lyon Sud)

Exclusion Criteria:

  • Multiorgan transplantation
  • Previous transplantation
  • ABO incompatible renal transplantation
  • Patient > 18 years old but under guardianship
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02843295
Other Study ID Numbers  ICMJE 2009-592
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Hospices Civils de Lyon
Study Sponsor  ICMJE Hospices Civils de Lyon
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Olivier THAUNAT, MD Hospices Civils de Lyon - Transplantation Department
PRS Account Hospices Civils de Lyon
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP