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

Disorder Related to Renal Transplantation Clinical Trial

— GABII  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02843841
• Other study ID #: P/2014/221
• Status: Active, not recruiting
• Phase: N/A
• First received: July 19, 2016
• Last updated: January 30, 2017
• Start date: December 2014
• Est. completion date: March 1, 2017

Study information

• Verified date: July 2016
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 63
• Est. completion date: March 1, 2017
• Est. primary completion date: March 1, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Disorder Related to Renal Transplantation

Intervention

Other:
• Blood and fecal sample.
Blood (28 ml) and fecal sample at day 0, 4 days, 3 months and one year after transplantation

Locations

Country	Name	City	State
France	Besancon University Hospital	Besançon

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	The serum levels of inflammatory cytokines (IL-1ß, IL-6, TNF-a, 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
Secondary	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
Secondary	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
Secondary	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
Secondary	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