Catalytic Antibodies to Predict Uninvasively Late Transplant Failure

Renal Transplantation Clinical Trial

— CATAPULT  

Official title:

Catalytic Antibodies to Predict Uninvasively Late Transplant Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02843295
• Other study ID #: 2009-592
• Status: Completed
• Phase: N/A
• First received: July 21, 2016
• Last updated: August 24, 2016
• Start date: September 2010
• Est. completion date: September 2015

Study information

• Verified date: August 2016
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Renal Transplantation

Intervention

Other:
• blood samples

Locations

Country	Name	City	State
France	Transplantation Department	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFR-MCA hydrolysis by circulating IgG (mmol/min/mol)		at 3 months post-transplantation	No
Primary	PFR-MCA hydrolysis by circulating IgG (mmol/min/mol)		at 6 months post-transplantation	No
Primary	PFR-MCA hydrolysis by circulating IgG (mmol/min/mol)		at 9 months post-transplantation	No
Primary	PFR-MCA hydrolysis by circulating IgG (mmol/min/mol)		at 12 months post-transplantation	No
Primary	PFR-MCA hydrolysis by circulating IgG (mmol/min/mol)		at 18 months post-transplantation	No
Primary	PFR-MCA hydrolysis by circulating IgG (mmol/min/mol)		at 24 months post-transplantation	No
Secondary	Glomerular filtration rate by MDRD formula (ml/min)		at 3 months post-transplantation	No
Secondary	Glomerular filtration rate by MDRD formula (ml/min)		at 6 months post-transplantation	No
Secondary	Glomerular filtration rate by MDRD formula (ml/min)		at 9 months post-transplantation	No
Secondary	Glomerular filtration rate by MDRD formula (ml/min)		at 12 months post-transplantation	No
Secondary	Glomerular filtration rate by MDRD formula (ml/min)		at 18 months post-transplantation	No
Secondary	Glomerular filtration rate by MDRD formula (ml/min)		at 24 months post-transplantation	No
Secondary	Proteinuria/creatinuria ratio (g/g)		at 3 months post-transplantation	No
Secondary	Proteinuria/creatinuria ratio (g/g)		at 6 months post-transplantation	No
Secondary	Proteinuria/creatinuria ratio (g/g)		at 9 months post-transplantation	No
Secondary	Proteinuria/creatinuria ratio (g/g)		at 12 months post-transplantation	No
Secondary	Proteinuria/creatinuria ratio (g/g)		at 18 months post-transplantation	No
Secondary	Proteinuria/creatinuria ratio (g/g)		at 24 months post-transplantation	No
Secondary	Interstitial fibrosis on graft biopsy (%)		at day 0	No
Secondary	Interstitial fibrosis on graft biopsy (%)		at 12 months post-transplantation	No
Secondary	Interstitial fibrosis on graft biopsy (%)		at 24 months post-transplantation	No