Ignite Creation Date:
2024-05-06 @ 4:17 PM
Last Modification Date:
2024-10-26 @ 2:07 PM
Study NCT ID:
NCT04934527
Status:
RECRUITING
Last Update Posted:
2023-07-18
First Post:
2021-04-16
Brief Title:
Association of T Gamma Delta-CD16 Cells and Anti-CMV Immunoglobulins in the Prevention of CMV Infection
Sponsor:
University Hospital Bordeaux
Organization:
University Hospital Bordeaux
Study Overview
Official Title:
Evaluating a Therapeutic Association Between CMV-specific Immunoglobulin Infusion and Pre-transplant CD16-expressing Gamma Delta Vdelta 2 Negative T-cells in CMV-positive Patients for Preventive Treatment of CMV Infection in Renal Transplantation
Status:
RECRUITING
Status Verified Date:
2023-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SYNTAGME
Brief Summary:
CMV infection in transplantation remains the most frequent infectious complication causing increased morbidity and mortality International recommendations advocate prevention of this infection by instituting direct antiviral treatment or monitoring viral replication by PCR with the start of curative antiviral treatment when the DNAemia is positive
The risk of CMV infection varies according to the serostatus of the donor D and recipient R at the time of transplantation In the absence of prophylaxis CMV infection occurs in 60-80 of DR- 50-60 of DR and 25-50 of D-R
The humoral anti-CMV response is represented by the production of antibodies to envelope proteins gB and gH and to molecules involved in viral attachment and entry into target cells However the majority of CMV-specific antibodies do not have antiviral neutralising activity The investigators have identified a new player in the specific anti-CMV response expressing the Fc RIIIa receptor CD16 that interacts with anti-CMV immunoglobulins Ig the Tgamma-delta V delta 2-negative lymphocyte LTgdVd2neg This lymphocyte subpopulation shows persistent expansion in the peripheral blood of kidney transplant patients with CMV infection These cells express an effector-memory phenotype CD45RACD27- This expansion is associated with resolution of infection in patients The investigators have shown that CD16 is specifically and constitutively expressed on the surface of CMV-induced LTgdVd2neg in healthy volunteers and kidney transplant patients The investigators have observed that one of the antiviral activities of anti-CMV IgG lies in its binding to the Fc RIIIa receptor CD16 on the surface of LTgdVd2neg The anti-CMV IgGs capturing virions thus activate CD16 LTgdVd2neg with production of IFN interferon which in turn is responsible for inhibition of CMV viral multiplication
Anti-CMV IgG is a recommended therapeutic option with a marketing authorisation for the prevention of CMV infection in kidney transplantation in Europe and a Temporary Authorisation for Use in France
Thus R patients expressing a significant level of LTgdVd2neg CD16 at D0 of transplantation could be protected against CMV in the absence of direct antiviral treatment by the addition of anti-CMV Ig
The risk of CMV infection varies according to the serostatus of the donor D and recipient R at the time of transplantation In the absence of prophylaxis CMV infection occurs in 60-80 of DR- 50-60 of DR and 25-50 of D-R
The humoral anti-CMV response is represented by the production of antibodies to envelope proteins gB and gH and to molecules involved in viral attachment and entry into target cells However the majority of CMV-specific antibodies do not have antiviral neutralising activity The investigators have identified a new player in the specific anti-CMV response expressing the Fc RIIIa receptor CD16 that interacts with anti-CMV immunoglobulins Ig the Tgamma-delta V delta 2-negative lymphocyte LTgdVd2neg This lymphocyte subpopulation shows persistent expansion in the peripheral blood of kidney transplant patients with CMV infection These cells express an effector-memory phenotype CD45RACD27- This expansion is associated with resolution of infection in patients The investigators have shown that CD16 is specifically and constitutively expressed on the surface of CMV-induced LTgdVd2neg in healthy volunteers and kidney transplant patients The investigators have observed that one of the antiviral activities of anti-CMV IgG lies in its binding to the Fc RIIIa receptor CD16 on the surface of LTgdVd2neg The anti-CMV IgGs capturing virions thus activate CD16 LTgdVd2neg with production of IFN interferon which in turn is responsible for inhibition of CMV viral multiplication
Anti-CMV IgG is a recommended therapeutic option with a marketing authorisation for the prevention of CMV infection in kidney transplantation in Europe and a Temporary Authorisation for Use in France
Thus R patients expressing a significant level of LTgdVd2neg CD16 at D0 of transplantation could be protected against CMV in the absence of direct antiviral treatment by the addition of anti-CMV Ig
Detailed Description:
SYNTAGME is a single-centre prospective phase II pilot study Transplant candidates from our centre who meet the inclusion criteria without exclusion criteria will be offered this study Anti-CMV Ig infusions will be performed the day of transplantation at 100 units per kilo of body weight and then every 15 days for a total of 6 infusions
Systematic and frequent monitoring for the occurrence of CMV DNAemia will be performed throughout this study Real-time quantitative CMV PCR on whole blood WHO standard provided by the National Institute for Biological Standards and Control will be performed every week until M3 then every fortnight until 4 months and then at months 5 6 9 and 12 CMV infection will be defined by the presence of a positive CMV PCR in whole blood Universal prophylaxis with VALGANCICLOVIR will be prohibited
Pre-emptive antiviral treatment will be initiated in case of CMV infection if the DNAemia reaches the threshold chosen by the centre which is 5000 IUml The choice of treatment will be left to the discretion of the clinician IV ganciclovir 5mgKg12H or valganciclovir 900mg12H until viral replication is negated Doses will be adjusted for kidney function using the Cockcroft-Gault formula in accordance with laboratory recommendations
Systematic and frequent monitoring for the occurrence of CMV DNAemia will be performed throughout this study Real-time quantitative CMV PCR on whole blood WHO standard provided by the National Institute for Biological Standards and Control will be performed every week until M3 then every fortnight until 4 months and then at months 5 6 9 and 12 CMV infection will be defined by the presence of a positive CMV PCR in whole blood Universal prophylaxis with VALGANCICLOVIR will be prohibited
Pre-emptive antiviral treatment will be initiated in case of CMV infection if the DNAemia reaches the threshold chosen by the centre which is 5000 IUml The choice of treatment will be left to the discretion of the clinician IV ganciclovir 5mgKg12H or valganciclovir 900mg12H until viral replication is negated Doses will be adjusted for kidney function using the Cockcroft-Gault formula in accordance with laboratory recommendations
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None