Using mTOR Inhibitors in the Prevention of BK Nephropathy

NCT01649609

Last updated date
Study Location
Columbia University Medical Center
New York, New York, 10032, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
BK Viremia, BK Nephropathy
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Renal transplant recipients age 18 years or over

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- Patients with multiorgan transplants


- Patients on immunosuppressive regimens that include steroids or Sirolimus at the time
of detection of viremia


- ABO incompatible renal transplants


- Three or more previous renal transplants


- Patients with contraindications to tacrolimus, sirolimus, mycophenolate mofetil or
mycophenolic acid.

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BK Viremia, BK NephropathyUsing mTOR Inhibitors in the Prevention of BK Nephropathy
NCT01649609
  1. New York, New York
  2. New York, New York
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Using mTOR Inhibitors in the Prevention of BK Nephropathy
Official Title  ICMJE Using mTOR Inhibitors in the Prevention of BK Nephropathy
Brief Summary BK virus infections after kidney transplant are increasing and can result in damage to the transplanted kidney. Currently, the universally accepted treatment is to decrease the strength of the antirejection medications but it is unclear what medications should be lowered and to what extent. The investigators propose to perform a study with patients who have BK virus detected in their blood during routine screening that appears to be increasing. The investigators will use two different strategies that involve different combinations of standard anti-rejection medications at lower dosages. Patients will be assigned to one of the two groups in a random manner across the two hospitals participating in the study. Patients will be followed for at least a year to determine if one strategy was more effective than the other in preventing an increase in the number of viruses in the blood stream and whether either one was more effective in reducing the negative impact of the infection on the functioning of the transplanted kidney.
Detailed Description

The incidence of BK viremia, an early complication after renal transplantation and the associated rates of graft loss resulting from BK nephropathy have been steadily rising since a series of cases that were reported in the mid-1990's. While this is at least partly related to the introduction of newer immunosuppressive agents, recent United Network for Organ Sharing (UNOS) data analyses suggest that there is a continuing rise in the incidence of BK viremia and associated nephropathy with a 3.5% incidence rate in 2009 representing a dramatic rise from just 0.9% only 4 years earlier. Single center data reports have suggested much lower rates of BK viremia and nephropathy in cohorts treated with mTOR (mammalian target of rapamycin) based immunosuppressive regimens when compared to the overall national incidence rates. Recent data has demonstrated that calcineurin inhibitors at concentrations routinely used in clinical practice interfere with the BK virus specific T cell responses; an interference that is not seen to occur with mTOR inhibitors. Further, recent evidence that inhibition of the mTOR pathway has a direct and consequential negative impact on BK infected cells provides additional insight into the observed benefit associated with mTOR inhibitors. The growing problem of BK viremia among renal transplant patients is further compounded by the absence of effective management strategies that have been tested in a rigorous or controlled setting - a fact that was highlighted in a recent systematic review. The cornerstone for management so far has been the reduction of immunosuppression, largely based on the outcome of a single center study of screening patients for viremia and following with preemptive lowering of immunosuppression. Conversion from calcineurin inhibitors to mTOR inhibitors has been reported in small case series to be an effective measure that appears to be superior to merely lowering immunosuppression; however, this approach has not been tested with a robust clinical study design.

Currently, the diagnosis of BK nephropathy requires a renal biopsy, an invasive procedure with its own risks. In addition, identification of patients with viremia who progress to nephropathy and subsequent graft failure i.e. prognostication does not appear possible with the renal biopsy results at present. Validation of potential non-invasive biomarkers provides a unique opportunity for both detection and risk stratification of patients with BK viremia subsequent failure, which could lead to more informed therapeutic interventions while supporting the development of newer therapies.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • BK Viremia
  • BK Nephropathy
Intervention  ICMJE
  • Drug: Tacrolimus
    Reduction of standard immunosuppression - The standard of care immunosuppression treatment commonly used for renal transplant patients
    Other Name: Prograf
  • Drug: Mycophenolate acid
    Myfortic or CellCept - The standard of care immunosuppression treatment most commonly used for renal transplant patients
    Other Name: mycophenolate antimetabolite
  • Drug: Sirolimus
    mTOR Substitution - Replacing tacrolimus (a calcineurin inhibitor) with sirolimus (an mTOR inhibitor) along with reduction of mycophenolic acid
    Other Name: Rapamune
Study Arms  ICMJE
  • Active Comparator: Reduction of standard immunosuppression
    Low dose Tacrolimus with low dose Mycophenolate acid
    Interventions:
    • Drug: Tacrolimus
    • Drug: Mycophenolate acid
  • Active Comparator: mTOR Arm
    Low dose Sirolimus with low dose Mycophenolate acid (mTOR Substitution)
    Interventions:
    • Drug: Mycophenolate acid
    • Drug: Sirolimus
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 31, 2018)
40
Original Estimated Enrollment  ICMJE
 (submitted: July 24, 2012)
60
Actual Study Completion Date  ICMJE December 2016
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Renal transplant recipients age 18 years or over

Exclusion Criteria:

  • Patients with multiorgan transplants
  • Patients on immunosuppressive regimens that include steroids or Sirolimus at the time of detection of viremia
  • ABO incompatible renal transplants
  • Three or more previous renal transplants
  • Patients with contraindications to tacrolimus, sirolimus, mycophenolate mofetil or mycophenolic acid.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01649609
Other Study ID Numbers  ICMJE AAAI9004
WS2036051 ( Other Identifier: Pfizer )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sumit Mohan, MD, Columbia University
Study Sponsor  ICMJE Columbia University
Collaborators  ICMJE
  • Pfizer
  • Cornell University
Investigators  ICMJE
Principal Investigator:Sumit Mohan, MDColumbia University
PRS Account Columbia University
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP