Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02843841
Recruitment Status : Unknown
Verified July 2016 by Centre Hospitalier Universitaire de Besancon.
Recruitment status was:  Active, not recruiting
First Posted : July 26, 2016
Last Update Posted : January 31, 2017
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Besancon

Brief 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.


Condition or disease Intervention/treatment Phase
Disorder Related to Renal Transplantation Other: Blood and fecal sample. Not Applicable

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 63 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Polyclonal Antilymphocyte Globulin (ATG) & Intestinal Immune Barrier After Kidney Transplantation
Study Start Date : December 2014
Actual Primary Completion Date : March 1, 2016
Estimated Study Completion Date : March 1, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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

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




Primary Outcome Measures :
  1. Serum LPS rate [ Time Frame: 1 year ]
    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.


Secondary Outcome Measures :
  1. The serum levels of LPS. [ Time Frame: 0, 4 days and 3 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).

  2. The serum levels of translocation marker and intestinal integrity (CD14, citrulline, LBP, CETP, PLTP, IFABP) [ Time Frame: 0, 4 days, 3 months and one year after transplantation ]
    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).

  3. The serum levels of inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-8, IL 12, CRP) [ Time Frame: 0, 4 days, 3 months and one year after transplantation ]
    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).

  4. The serum levels of regeneration cytokines (IL-7, IL-15 and IL-22) [ Time Frame: 0, 4 days, 3 months and one year after transplantation ]
    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).

  5. 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 [ Time Frame: 0, 4 days, 3 months and one year after transplantation ]
    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).

  6. TLR-4 polymorphism [ Time Frame: 0, 4 days, 3 months and one year after transplantation ]
    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,

  7. The composition of the intestinal microbiota. [ Time Frame: 0, 4 days, 3 months and one year after transplantation ]
    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,



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02843841


Locations
Layout table for location information
France
Besancon University Hospital
Besançon, France, 25030
Sponsors and Collaborators
Centre Hospitalier Universitaire de Besancon
Investigators
Layout table for investigator information
Principal Investigator: Jamal Bamoulid, Dr. Besancon University Hospital - Nephrology departement
Layout table for additonal information
Responsible Party: Centre Hospitalier Universitaire de Besancon
ClinicalTrials.gov Identifier: NCT02843841    
Other Study ID Numbers: P/2014/221
First Posted: July 26, 2016    Key Record Dates
Last Update Posted: January 31, 2017
Last Verified: July 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No