title: The Calcineurin Inhibitor-Sparing (CIS) Trial - individualised calcineurin-inhibitor treatment by immunomonitoring in renal allograft recipients: protocol for a randomised controlled trial.
abstract: BACKGROUND
  Adequate monitoring tools are required to optimise the immunosuppressive therapy of an individual patient. Particularly, in calcineurin inhibitors, as critical dose drugs with a narrow therapeutic range, the optimal monitoring strategies are discussed in terms of safety and efficacy. Nevertheless, no pharmacokinetic monitoring markers reflect the biological activity of the drug. A new quantitative analysis of gene expression was employed to directly measure the functional effects of calcineurin inhibition: the transcriptional activities of the nuclear factor of activated T-cell (NFAT)-regulated genes in the peripheral blood.
  
  
  METHODS
  The CIS study is a randomised prospective controlled trial, comparing a ciclosporin A (CsA)-based immunosuppressive regimen monitored by CsA trough levels to a CsA-based immunosuppressive regimen monitored by residual NFAT-regulated gene expression. Pulse wave velocity as an accepted surrogate marker of the cardiovascular risk is assessed in both study groups. Our hypothesis is that an individualised CsA therapy monitored by residual NFAT-regulated gene expression results in a significantly lower cardiovascular risk compared to CsA therapy monitored by CsA trough levels.
  
  
  CONCLUSIONS
  There is a lack of evidence in individualising standard immunosuppression in renal allograft recipients. The CIS study will consider the feasibility of individualised ciclosporin A immunosuppression by pharmacodynamic monitoring and evaluate the opportunity to reduce cardiovascular risk while maintaining sufficient immunosuppression.
  
  
  BACKGROUND
  EudraCT identifier 2011-003547-21, registration date 18 July 2011https://www.clinicaltrialsregister.eu.
authors.affiliation: Department of Nephrology, University Hospital Heidelberg, Im Neuenheimer Feld 162, D-69120 Heidelberg, Germany. Claudia.Sommerer@med.uni-heidelberg.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommerer
authors.forename: Matthias
authors.initials: M
authors.lastname: Schaier
authors.forename: Christian
authors.initials: C
authors.lastname: Morath
authors.forename: Vedat
authors.initials: V
authors.lastname: Schwenger
authors.forename: Geraldine
authors.initials: G
authors.lastname: Rauch
authors.forename: Thomas
authors.initials: T
authors.lastname: Giese
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
mesh_terms: D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D002985:Clinical Protocols; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D016903:Drug Monitoring / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D005858:Germany; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D016030:Kidney Transplantation / Q000009:adverse effects; D015166:Monitoring, Immunologic; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D011237:Predictive Value of Tests; D011446:Prospective Studies; D063177:Pulse Wave Analysis; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D050778:NFATC Transcription Factors; D016572:Cyclosporine