Catalytic Antibodies to Predict Uninvasively Late Transplant Failure (CATAPULT)

August 24, 2016 updated by: Hospices Civils de Lyon
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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lyon, France, 69003
        • Transplantation Department

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Other: blood samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
PFR-MCA hydrolysis by circulating IgG (mmol/min/mol)
Time Frame: at 3 months post-transplantation
at 3 months post-transplantation
PFR-MCA hydrolysis by circulating IgG (mmol/min/mol)
Time Frame: at 6 months post-transplantation
at 6 months post-transplantation
PFR-MCA hydrolysis by circulating IgG (mmol/min/mol)
Time Frame: at 9 months post-transplantation
at 9 months post-transplantation
PFR-MCA hydrolysis by circulating IgG (mmol/min/mol)
Time Frame: at 12 months post-transplantation
at 12 months post-transplantation
PFR-MCA hydrolysis by circulating IgG (mmol/min/mol)
Time Frame: at 18 months post-transplantation
at 18 months post-transplantation
PFR-MCA hydrolysis by circulating IgG (mmol/min/mol)
Time Frame: at 24 months post-transplantation
at 24 months post-transplantation

Secondary Outcome Measures

Outcome Measure
Time Frame
Glomerular filtration rate by MDRD formula (ml/min)
Time Frame: at 3 months post-transplantation
at 3 months post-transplantation
Glomerular filtration rate by MDRD formula (ml/min)
Time Frame: at 6 months post-transplantation
at 6 months post-transplantation
Glomerular filtration rate by MDRD formula (ml/min)
Time Frame: at 9 months post-transplantation
at 9 months post-transplantation
Glomerular filtration rate by MDRD formula (ml/min)
Time Frame: at 12 months post-transplantation
at 12 months post-transplantation
Glomerular filtration rate by MDRD formula (ml/min)
Time Frame: at 18 months post-transplantation
at 18 months post-transplantation
Glomerular filtration rate by MDRD formula (ml/min)
Time Frame: at 24 months post-transplantation
at 24 months post-transplantation
Proteinuria/creatinuria ratio (g/g)
Time Frame: at 3 months post-transplantation
at 3 months post-transplantation
Proteinuria/creatinuria ratio (g/g)
Time Frame: at 6 months post-transplantation
at 6 months post-transplantation
Proteinuria/creatinuria ratio (g/g)
Time Frame: at 9 months post-transplantation
at 9 months post-transplantation
Proteinuria/creatinuria ratio (g/g)
Time Frame: at 12 months post-transplantation
at 12 months post-transplantation
Proteinuria/creatinuria ratio (g/g)
Time Frame: at 18 months post-transplantation
at 18 months post-transplantation
Proteinuria/creatinuria ratio (g/g)
Time Frame: at 24 months post-transplantation
at 24 months post-transplantation
Interstitial fibrosis on graft biopsy (%)
Time Frame: at day 0
at day 0
Interstitial fibrosis on graft biopsy (%)
Time Frame: at 12 months post-transplantation
at 12 months post-transplantation
Interstitial fibrosis on graft biopsy (%)
Time Frame: at 24 months post-transplantation
at 24 months post-transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Investigators

  • Principal Investigator: Olivier THAUNAT, MD, Hospices Civils de Lyon - Transplantation Department

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2010

Primary Completion (Actual)

September 1, 2015

Study Completion (Actual)

September 1, 2015

Study Registration Dates

First Submitted

July 21, 2016

First Submitted That Met QC Criteria

July 22, 2016

First Posted (Estimate)

July 25, 2016

Study Record Updates

Last Update Posted (Estimate)

August 25, 2016

Last Update Submitted That Met QC Criteria

August 24, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 2009-592

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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