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Secondary Prophylaxis After CMV Disease in Kidney Transplant Patients Targeted by γδ T Cells Immunomonitoring. (SPARCKLING)

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ClinicalTrials.gov Identifier: NCT03339661
Recruitment Status : Recruiting
First Posted : November 13, 2017
Last Update Posted : November 28, 2017
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux

Brief Summary:
In kidney transplant patients, CMV infection remains the leading infectious cause of morbidity and mortality. Clinical and virological relapses are common and are involved in chronic graft dysfunction. To date, it is not certain that secondary prophylaxis allows reducing these relapses, although this prophylaxis is part of the current recommendations. Our team has recently shown that the expansion of γδ T cells in peripheral blood during CMV infection was correlated with the absence of virological and clinical relapses. Indeed, the absence of relapse was associated in 94.7% of cases with the presence of γδ T cells expansion while relapses occurred in about 90% of cases in the absence of γδ T cells expansion. These results suggest that the indication and duration of secondary prophylaxis after the curative treatment of CMV infection in kidney transplantation could be guided by the immune surveillance of γδ T cells.

Condition or disease Intervention/treatment Phase
Kidney Transplant Infection Drug: Group 1_No proph treatment Drug: Group 2A_Proph treatment and γδ T cell expansion Drug: Group 2B_Proph treatment and no γδ T cell expansion Phase 2

Detailed Description:

The study aim to demonstrate that the expansion of γδ T cells at the end of curative treatment predicts the absence of virological and clinical relapses. This is a pilot study that will be conducted in the transplant center of Bordeaux and Lyon. After the curative treatment of CMV infection until a negative CMV ADNemia, secondary prophylaxis with valganciclovir will be established based on the results of γδ T cells immunomonitoring:

(I) Secondary prophylaxis will not be started in patients with γδ T cell expansion at the end of curative treatment (group 1) (II) Secondary prophylaxis will be initiated in patients who have not γδ T cell expansion and will continue for 3 months maximum. The occurrence of γδ T cells expansion during or at the end of secondary prophylaxis will define the group 2A. Patients who still not had γδ T cells expansion during or at the end of secondary prophylaxis will compose the group 2B.

The primary outcome of this study will be to evaluate the occurrence of virological relapse, assessed by monitoring CMV ADNemia, at one year of a first CMV disease, in kidney transplant patients, with secondary prophylaxis based on the monitoring of γδ T cells.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 37 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Secondary Prophylaxis After CMV Disease in Kidney Transplant Patients Targeted by γδ T
Actual Study Start Date : November 23, 2017
Estimated Primary Completion Date : November 23, 2019
Estimated Study Completion Date : November 23, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group 1_ No proph treatment
Patients will receive a curative treatment (ganciclovir or valganciclovir, drug administrated will depend on medical opinion) during 2 to 8 weeks. When CMV QNAT becomes regative, if γδ T cell expansion occurs, no secondary prophylaxis treatment will be introduce, and curative treatment stops.
Drug: Group 1_No proph treatment
After the curative treatment of CMV infection until a negative CMV ADNemia, secondary prophylaxis with valganciclovir will be established based on the results of γδ T cells immunomonitoring. In this group, expansion of γδ T cell at the end curative treatment was detected, so secondary prophylaxis will not be started.

Experimental: Group 2A_Proph treatment and γδ T cells expansion
Patients will receive a curative treatment (ganciclovir or valganciclovir, drug administrated depends on medical opinion) during 2 to 8 weeks. When CMV QNAT becomes regative, if no γδ T cell expansion will occur, a secondary prophylaxis will be initiated during 3 months maximum. The occurrence of γδ T cells expansion during or at the end of secondary prophylaxis will define the group 2A.
Drug: Group 2A_Proph treatment and γδ T cell expansion
After the curative treatment of CMV infection until a negative CMV ADNemia, secondary prophylaxis with valganciclovir will be established based on the results of γδ T cells immunomonitoring. In this group, γδ T cell expansion will not be detected, so secondary prophylaxis will be initiated in continue during 3 months maximum. The occurrence of γδ T cells expansion during or at the end of secondary prophylaxis will define the group 2A.

Experimental: Group 2B_Proph treatment and no γδ T cells expansion
Patients will receive a curative treatment (ganciclovir or valganciclovir, drug administrated depends on medical opinion) during 2 to 8 weeks. When CMV QNAT becomes regative, if no γδ T cell expansion will occur, a secondary prophylaxis will be initiated during 3 months maximum. Patients who still not had γδ T cells expansion during or at the end of secondary prophylaxis will compose the group 2B.
Drug: Group 2B_Proph treatment and no γδ T cell expansion
After the curative treatment of CMV infection until a negative CMV ADNemia, secondary prophylaxis with valganciclovir will be established based on the results of γδ T cells immunomonitoring. In this group, γδ T cell expansion will not be detected, so secondary prophylaxis will be initiated in continue during 3 months maximum. Patients who still not had γδ T cells expansion during or at the end of secondary prophylaxis will compose the group 2B.




Primary Outcome Measures :
  1. Assessment of virological relapse occurence [ Time Frame: 12 months after inclusion visit ]
    The primary outcome of this study will be to evaluate the occurrence of virological relapse, assessed by monitoring CMV ADNemia.


Secondary Outcome Measures :
  1. Cumulative incidence of clinical recurrence [ Time Frame: 12 months after inclusion visit ]
    Cumulative incidence of clinical recurrence defined by a positive CMV PCR associated with clinical and biological signs of CMV disease. This incidence is expressed as a percentage of the total number of patients with CMV infection included.

  2. γδ T cells expansion dynamic [ Time Frame: 12 months after the inclusion visit ]
    Description of the dynamics of γδ T cells expansion in all patients. At each visit, an immunophenotyping with analysis of the percentage of γδ T cells will be performed.

  3. Cumulative incidence of clinical recurrence at discontinuation of prophylaxis. [ Time Frame: 12 months after the inclusion visit ]
    These incidences will be expressed as a percentage of the total number of patients who have had CMV infection included. Recidivism will be collected by the investigating physician when observed during a follow-up visit.

  4. Cumulative incidence of virological recurrence at discontinuation of prophylaxis. [ Time Frame: 12 months after inclusion visit ]
    These incidences will be expressed as a percentage of the total number of patients who have had CMV infection included. Recidivism will be collected by the investigating physician when observed during a follow-up visit.

  5. secondary prophylaxis duration [ Time Frame: 12 months after inclusion visit ]
    The duration of the secondary prophylaxis is defined by the duration of treatment since the stop of the curative treatment until the stop of the prophylactic treatment.

  6. Prophylaxis treatment savings evaluation [ Time Frame: 12 months after inclusion visit ]
    Evaluation of prophylaxis treatment savings (compared to a one-month prophylaxis) by number of subject and average total duration (with standard deviation) of treatment.

  7. Proportion of antiviral resistant infections [ Time Frame: 12 months after inclusion visit ]
    the proportion of antiviral resistant infections confirmed by genotypic analysis (mutations UL97 and UL54) sought during recurrence in case of clinical suspicion.

  8. GFR average [ Time Frame: 12 months after inclusion visit ]
    GFR average and its standard deviation are estimated according to MDRD formula

  9. Compliance rate [ Time Frame: 12 months after inclusion visit ]
    The compliance rate will, be performed by a patient notebook.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female over 18 years old without weight or ethnicity criteria, kidney transplant.
  • Patient affiliated or beneficiary of a social security scheme.
  • Patient with symptomatic or non-symptomatic CMV infection requiring curative treatment with ganciclovir or valganciclovir.
  • Free, informed and written consent signed by the participant and the investigator (at the latest, on the day of inclusion and before any examination required by the research).

Exclusion Criteria:

  • Resistance documented to antivirals.
  • Hemodialysis patient.
  • Number of polymorphonuclear neutrophils less than 500 / μL and / or number of platelets less than 25,000 / μL, and / or lower hemoglobin 8 g / dL.
  • Contraindication to valganciclovir, including known hypersensitivity to valganciclovir and / or aciclovir and / or valaciclovir or ganciclovir or their excipients, known severe intolerance to valganciclovir or ganciclovir.
  • Women of childbearing age without a negative pregnancy test at baseline and without effective contraception (estrogen-progestin, intrauterine device) throughout the study period and two months after cessation of the follow-up period.
  • Nursing women.
  • Men without mechanical contraception during treatment and for at least 90 days after treatment.
  • Ongoing participation in another clinical trial evaluating a drug. Participation in an observational study will not be considered a contraindication.
  • The patient's foreseeable inability to comply with planned visits in the protocol.
  • Non-negativation of CMV PCR at 8 weeks

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): NCT03339661


Contacts
Contact: Hannah KAMINSKI, Dr 05 56 79 54 49 ext +33 hannah.kaminski@chu-bordeaux.fr
Contact: Lionel COUZI, Pr lionel.couzi@chu-bordeaux.fr

Locations
France
Hôpital Pellegrin - CHU de Bordeaux Recruiting
Bordeaux, France, 33000
Contact: Hannah KAMINSKI, Dr    05 56 79 54 49 ext +33    hannah.kaminski@chu-bordeaux.fr   
Contact: Lionel COUZI, Pr       lionel.couzi@chu-bordeaux.fr   
Sub-Investigator: Pierre MERVILLE, Pr         
Principal Investigator: Hannah KAMINSKI, Dr         
Sub-Investigator: Lionel COUZI, Pr         
Hôpital Edouard Herriot - Hospices Civils de Lyon Not yet recruiting
Lyon, France, 69003
Contact: Olivier Thaunat    04-27-85-80-72 ext +33    olivier.thaunat@chu-lyon.fr   
Contact: Emmanuel Morelon    04-27-85-80-72    emmanuel.morelon@chu-lyon.fr   
Principal Investigator: Olivier Thaunat         
Sub-Investigator: Emmanuel Morelon         
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
Study Chair: Edouard LHOMME, Dr USMR

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT03339661     History of Changes
Other Study ID Numbers: CHUBX 2016/40
First Posted: November 13, 2017    Key Record Dates
Last Update Posted: November 28, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Bordeaux:
CMV infection
kidney transplant
γδ T cells monitoring

Additional relevant MeSH terms:
Valganciclovir
Antiviral Agents
Anti-Infective Agents