Polyclonal Antilymphocyte Globulin (ATG) & Intestinal Immune Barrier After Kidney Transplantation (GABII)

The prevention of allograft rejection in kidney transplantation requires administering to the patient an immunosuppressive regimen of induction. The induction strategy is based on an injection of polyclonal anti-lymphocyte globulin (ATG-FLAG or fresenius®) driving a lymphocyte lysis, or an injection of monoclonal antibodies directed against non-lymphopenic the α chain of the IL-receptor 2 (anti-CD25 antibody, basiliximab), by immunological risk patients. Our group showed a significant increase in death rates in transplant patients with lymphopenia CD4 continued beyond 2 years of transplantation. This excess mortality is related to complications following chronic inflammation observed in some patients lymphopenic.

Preliminary studies have shown that the induced lymphodéplétion ATG appears to be accompanied by an increase of the bacterial products in the blood of transplanted since a significant increase in the sCD14 is observed in these patients one year. We also observed increased concentrations of LPS in patients in the ATG group. This could indicate a secondary bacterial intestinal translocation to a weakening of intestinal immunity linked to the ATG.

The main objective of the study is to assess the impact of anti-lymphocyte globulin polyclonal on intestinal permeability, estimated by the rate lipopolysaccharide (LPS, a constituent of the cell wall of Gram-negative bacteria) blood after kidney transplantation.

The secondary objectives are to evaluate bacterial translocation, the effect of bacterial translocation on structural and metabolic functions of the intestinal epithelium, chronic inflammation, immune reconstitution, regeneration, activation and proliferation of T lymphocytes, the polymorphism of the LPS receptor that causes the activation of innate immunity and the composition of the intestinal microbiota.

The study population consists of renal transplant patients of Nephrology of the University Hospital of Besancon. Patients will be divided into 2 groups according to induction immunosuppressive therapy prescribed the day of renal transplantation as part of their usual care, ie treatment with anti-lymphocyte globulin polyclonal (ATG-Fresenius®) or antibody treatment monoclonal anti-CD25 (basiliximab Simulect). The patient group treated with anti-CD25 antibody will serve as a control group (no depletion of the immune system) to the group of patients treated with ATG.

Study Overview

• Status: Unknown
• Conditions: Disorder Related to Renal Transplantation
• Intervention / Treatment: Other: Blood and fecal sample.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Besançon, France, 25030
    • Besançon University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women aged 18 to 80 years included
• Postmenopausal women for at least 24 months, sterilized surgically, or for women of childbearing age, use an effective method of contraception (oral contraceptives, contraceptive injections, intrauterine devices, method of double-barrier contraceptive patches)
• Participation in the study ORLY East
• Signature of informed consent for participation indicating that the subject has understood the purpose and procedures required by the study and agrees to participate in the study and comply with the requirements and limitations inherent in this study
• Join a French social security or receiving such a plan

Exclusion Criteria:

• Legal incapacity or limited legal capacity
• Topic unlikely to cooperate in the study and / or low early cooperation by the investigator
• Without health insurance Topic
• Pregnant woman
• Inability to understand the reasons for the study; psychiatric disorders judged by the investigator to be incompatible with the inclusion in the study
• Infectious episode with need for hospitalization older than 1 month
• Active infection by the virus of hepatitis B and / or C
• Active infection by HIV or not
• Patients with inflammatory bowel disease (IBD)
• Patients who have undergone total colectomy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: ATG group; Renal transplant Patients from Nephrology department of the University Hospital of Besancon receiving induction immunosuppressive therapy of polyclonal antilymphocyte globulin (ATG-Fresenius®) as recommended. Intervention = blood and fecal sample	Other: Blood and fecal sample.; Blood (28 ml) and fecal sample at day 0, 4 days, 3 months and one year after transplantation
Other: Anti-CD25 group; PRenal transplant Patients from Nephrology department of the University Hospital of Besancon receiving induction immunosuppressive therapy of anti-CD25 monoclonal antibodies (basiliximab SIMULECT®) as recommended. Intervention = blood and fecal sample	Other: Blood and fecal sample.; Blood (28 ml) and fecal sample at day 0, 4 days, 3 months and one year after transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum LPS rate	LPS serum levels of kidney transplant patients treated with ATG evaluated by liquid chromatography coupled with mass spectroscopy before transplantation and 1 year after transplantation compared to renal transplant patients treated with anti-CD25 antibody.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The serum levels of LPS.	The results will be correlated to clinical data reported during the first year following the day of transplantation, namely: CMV disease, severe opportunistic infections bacterial infections, atherosclerotic events, dialysis back, patient treatment (antibiotics, standard treatment at the time of sampling).	0, 4 days and 3 months after transplantation
The serum levels of translocation marker and intestinal integrity (CD14, citrulline, LBP, CETP, PLTP, IFABP)	All secondary endpoints will be measured at 0, 4 days, 3 and 12 months after transplantation. The results will be correlated to clinical data reported during the first year following the day of transplantation, namely: CMV disease, severe opportunistic infections bacterial infections, atherosclerotic events, dialysis back, patient treatment (antibiotics, standard treatment at the time of sampling).	0, 4 days, 3 months and one year after transplantation
The serum levels of inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-8, IL 12, CRP)	All secondary endpoints will be measured at 0, 4 days, 3 and 12 months after transplantation. The results will be correlated to clinical data reported during the first year following the day of transplantation, namely: CMV disease, severe opportunistic infections bacterial infections, atherosclerotic events, dialysis back, patient treatment (antibiotics, standard treatment at the time of sampling).	0, 4 days, 3 months and one year after transplantation
The serum levels of regeneration cytokines (IL-7, IL-15 and IL-22)	All secondary endpoints will be measured at 0, 4 days, 3 and 12 months after transplantation. The results will be correlated to clinical data reported during the first year following the day of transplantation, namely: CMV disease, severe opportunistic infections bacterial infections, atherosclerotic events, dialysis back, patient treatment (antibiotics, standard treatment at the time of sampling).	0, 4 days, 3 months and one year after transplantation
Serum percentage of CD8+CD57+CD28- LT, CD31+CD4+CD45RA+ LT, Lin-CD34+CD45+CD10+CD38+CD117-CD45RA+ LT, CD3+CD4/8+HLADR+CD38+ LT, Ki67	All secondary endpoints will be measured at 0, 4 days, 3 and 12 months after transplantation. The results will be correlated to clinical data reported during the first year following the day of transplantation, namely: CMV disease, severe opportunistic infections bacterial infections, atherosclerotic events, dialysis back, patient treatment (antibiotics, standard treatment at the time of sampling).	0, 4 days, 3 months and one year after transplantation
TLR-4 polymorphism	All secondary endpoints will be measured at 0, 4 days, 3 and 12 months after transplantation. The results will be correlated to clinical data reported during the first year following the day of transplantation,	0, 4 days, 3 months and one year after transplantation
The composition of the intestinal microbiota.	All secondary endpoints will be measured at 0, 4 days, 3 and 12 months after transplantation. The results will be correlated to clinical data reported during the first year following the day of transplantation,	0, 4 days, 3 months and one year after transplantation

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon
• Investigators: Principal Investigator: Jamal Bamoulid, Dr., Besancon University Hospital - Nephrology departement

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): March 1, 2016
• Study Completion (Anticipated): March 1, 2017

Study Registration Dates

• First Submitted: July 19, 2016
• First Submitted That Met QC Criteria: July 21, 2016
• First Posted (Estimate): July 26, 2016

Study Record Updates

• Last Update Posted (Estimate): January 31, 2017
• Last Update Submitted That Met QC Criteria: January 30, 2017
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: P/2014/221

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO