Catalytic Antibodies to Predict Uninvasively Late Transplant Failure (CATAPULT)

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

Study Description

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

Condition or disease	Intervention/treatment	Phase
Renal Transplantation	Other: blood samples	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: Catalytic Antibodies to Predict Uninvasively Late Transplant Failure
• Study Start Date: September 2010
• Actual Primary Completion Date: September 2015
• Actual Study Completion Date: September 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. PFR-MCA hydrolysis by circulating IgG (mmol/min/mol) [ Time Frame: at 3 months post-transplantation ]
2. PFR-MCA hydrolysis by circulating IgG (mmol/min/mol) [ Time Frame: at 6 months post-transplantation ]
3. PFR-MCA hydrolysis by circulating IgG (mmol/min/mol) [ Time Frame: at 9 months post-transplantation ]
4. PFR-MCA hydrolysis by circulating IgG (mmol/min/mol) [ Time Frame: at 12 months post-transplantation ]
5. PFR-MCA hydrolysis by circulating IgG (mmol/min/mol) [ Time Frame: at 18 months post-transplantation ]
6. PFR-MCA hydrolysis by circulating IgG (mmol/min/mol) [ Time Frame: at 24 months post-transplantation ]

Secondary Outcome Measures :

1. Glomerular filtration rate by MDRD formula (ml/min) [ Time Frame: at 3 months post-transplantation ]
2. Glomerular filtration rate by MDRD formula (ml/min) [ Time Frame: at 6 months post-transplantation ]
3. Glomerular filtration rate by MDRD formula (ml/min) [ Time Frame: at 9 months post-transplantation ]
4. Glomerular filtration rate by MDRD formula (ml/min) [ Time Frame: at 12 months post-transplantation ]
5. Glomerular filtration rate by MDRD formula (ml/min) [ Time Frame: at 18 months post-transplantation ]
6. Glomerular filtration rate by MDRD formula (ml/min) [ Time Frame: at 24 months post-transplantation ]
7. Proteinuria/creatinuria ratio (g/g) [ Time Frame: at 3 months post-transplantation ]
8. Proteinuria/creatinuria ratio (g/g) [ Time Frame: at 6 months post-transplantation ]
9. Proteinuria/creatinuria ratio (g/g) [ Time Frame: at 9 months post-transplantation ]
10. Proteinuria/creatinuria ratio (g/g) [ Time Frame: at 12 months post-transplantation ]
11. Proteinuria/creatinuria ratio (g/g) [ Time Frame: at 18 months post-transplantation ]
12. Proteinuria/creatinuria ratio (g/g) [ Time Frame: at 24 months post-transplantation ]
13. Interstitial fibrosis on graft biopsy (%) [ Time Frame: at day 0 ]
14. Interstitial fibrosis on graft biopsy (%) [ Time Frame: at 12 months post-transplantation ]
15. Interstitial fibrosis on graft biopsy (%) [ Time Frame: at 24 months post-transplantation ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

France

Transplantation Department

Lyon, France, 69003

Sponsors and Collaborators

Hospices Civils de Lyon

Investigators

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

More Information

• Responsible Party: Hospices Civils de Lyon
• ClinicalTrials.gov Identifier: NCT02843295
• Other Study ID Numbers: 2009-592
• First Posted: July 25, 2016
• Last Update Posted: August 25, 2016
• Last Verified: August 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Hospices Civils de Lyon:

renal transplantation; immunology; rejection