Immune Monitoring and CNI Withdrawal in Low Risk Recipients of Kidney Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01517984
First received: January 20, 2012
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

Kidney transplantation is a good treatment option for people with kidney disease. However, there is still much to learn about how to best care for the transplanted kidney and keep it functioning for a long time. Transplant recipients take immunosuppression (anti-rejection) drugs to prevent their body from rejecting the new kidney. These drugs are used to prevent the immune system from attacking the transplanted kidney. All anti-rejection medications have unwanted side effects. The purpose of this study is to evaluate the safety of slowly removing tacrolimus therapy after treatment with ATG. The study will compare how well transplanted kidneys work and the response of people's immune systems as tacrolimus is stopped. In addition, this research study will evaluate whether reducing immunosuppression can decrease some of these side effects while still preventing rejection of the kidney.


Condition Intervention Phase
Kidney Transplant
Drug: Tacrolimus + MMF + Prednisone, followed by Tacrolimus Withdrawal
Drug: MMF/Tacrolimus/Prednisone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Immune Monitoring and Calcineurin Inhibitor (CNI) Withdrawal in Low Risk Recipients of Kidney Transplantation

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Percentage of patients with incremental IF/A scores >2 at 18 months post-randomization [ Time Frame: The IF/TA scores on protocol biopsies obtained at 18 months postrandomization will be compared to those obtained at the time of implantation for this measurement ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Estimated GFR using the Chronic Kidney Disease Epidemiology (CKD-EPI) equation [ Time Frame: 6 to 18 months post-randomization ] [ Designated as safety issue: Yes ]
  • Incidence of acute rejection [ Time Frame: 6 to 18 months post-randomization ] [ Designated as safety issue: Yes ]
  • Allograft survival rate [ Time Frame: 6 to 18 months post-randomization ] [ Designated as safety issue: Yes ]
  • Patient survival rate [ Time Frame: 6 to 18 months post-transplantation ] [ Designated as safety issue: Yes ]
  • Percentage of patients with new donor specific antibodies [ Time Frame: 6 to 18 months post-randomization ] [ Designated as safety issue: Yes ]
  • Percentage of patients with donor-specific memory using Elispot [ Time Frame: 6 to 18 months post-randomization ] [ Designated as safety issue: Yes ]
  • Percentage of patients in the experimental arm off tacrolimus [ Time Frame: 6 to 18 months post-randomization ] [ Designated as safety issue: Yes ]
  • Incremental change in IF/TA scores [ Time Frame: 6 to 18 months post-transplant ] [ Designated as safety issue: Yes ]
  • Measurement of urinary parameters (e.g., urinary chemokines and gene expression) before and after randomization [ Time Frame: 6 months post-transplant to 18 months post-randomization ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 210
Study Start Date: November 2010
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CNI Withdrawal Drug: Tacrolimus + MMF + Prednisone, followed by Tacrolimus Withdrawal
Active Comparator: Triple Immunosuppression Drug: MMF/Tacrolimus/Prednisone

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA -

Initial Enrollment/Screening: Patients who meet all of the following criteria are eligible for enrollment as study subjects.

  1. Subject must be able to understand and provide written informed consent;
  2. Male or Female, 18 years of age and older;
  3. Primary living-donor (related or unrelated) kidney transplant recipients;
  4. Peak flow-based PRAs for class I and class II <30%(performed by local center);
  5. Current (within 8 weeks prior to transplantation) flow-based PRAs for class I and class II <30% (performed by local center);
  6. No donor specific antibody by flow solid phase method on the peak PRA serum (if serum available), or on the current PRA serum (within 8 weeks prior to transplantation) performed by central core laboratory. If the sera for the peak PRA is not available, then only the current PRA serum will be tested;
  7. Negative T-cell and B-cell crossmatch by flow cytometry (performed by local center);
  8. Female subjects of childbearing potential must have a negative pregnancy test (urine or serum) upon study entry;
  9. Female and male subjects with reproductive potential must agree to use FDA approved methods of birth control while participating in the study.Inclusion Criteria for Randomization:

Patients who meet all of the following criteria are eligible for randomization:

  1. No history of acute rejection episodes;
  2. The pre-randomization protocol biopsy should confirm no rejection, including borderline rejection (based on the central pathology read);
  3. No donor specific antibody as detected by flow solid phase method (performed by the central core laboratory).

EXCLUSION CRITERIA -

Initial Enrollment/Screening:

Patients who meet any of these criteria are not eligible for enrollment as study subjects:

  1. Recipient of multiple organ transplants;
  2. Prior history of organ transplantation;
  3. Deceased-donor source;
  4. Any condition that would preclude protocol biopsies;
  5. HLA identical recipients;
  6. Currently breast-feeding or plans to become pregnant during the timeframe of the study follow up period;
  7. Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements;
  8. Inability or unwillingness of a subject to comply with study protocol;
  9. Use of investigational drugs within 4 weeks of study entry and for the duration of the study;
  10. Recent recipient of any licensed or investigational live attenuated vaccine(s) within two months of prior to study entry.

Exclusion Criteria for Randomization:

Patients who meet any of these criteria are not eligible for randomization:

  1. Subjects who receive less than 4.5mg/kg of Rabbit ATG (Thymoglobulin®) induction therapy;
  2. Subjects who test positive for BKV by PCR in the blood at 6 months post-transplant;
  3. Any condition that would preclude protocol biopsies;
  4. Currently breast-feeding or plans to become pregnant during the timeframe of the study follow up period;
  5. Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements;
  6. Inability or unwillingness of a subject to give written informed consent or comply with study protocol;
  7. Use of investigational drugs within 4 weeks of study entry and for the duration of the study.
  8. Subjects who receive less than 1500 mg daily of Mycophenolate Mofetil (CellCept®) or its equivalent.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01517984

Locations
United States, California
University of California Los Angeles Recruiting
Los Angeles, California, United States, 90055
Contact: Maria Morales    310-794-8516    mimorales@mednet.ucla.edu   
Principal Investigator: Suphamai Bunnapradist, MD         
United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06520-8029
Contact: Danielle (Lettieri) Jacques    203-785-7031    Danielle.Lettieri@yale.edu   
Contact: Ricarda Tomlin    203-785-2073    Ricarda.tomlin@yale.edu   
Principal Investigator: Richard Formica, Jr., MD         
United States, Massachusetts
Brigham & Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Christine Dyer-Ward, MA    617-732-8553    cdyer@partners.org   
Contact: Sarah Conte    617-732-8132    sconte@partners.org   
Principal Investigator: Anil Chandraker, MD         
United States, Michigan
University of Michigan Hospital Recruiting
Ann arbor, Michigan, United States, 48109
Contact: Jennifer Mawby    734-936-4811      
Principal Investigator: Milagros Samaniego, MD         
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Rebecca Skelton    314-362-4109      
Principal Investigator: Daniel Brennan, MD         
United States, New York
Mount Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Contact: Brandy Haydel    212-241-0255    Brandy.Haydel@mountsinai.org   
Contact: Sherif Mikhail    (212) 659-8039    sherif.mikhail@mountsinai.org   
Principal Investigator: Bernd Schroppel, MD         
United States, Ohio
University Hospitals of Cleveland Recruiting
Cleveland, Ohio, United States, 44106-5048
Contact: Tracey Lee    216-844-5396    Tracey.Lee@uhhospitals.org   
Contact: Victoria Rodriquez    (216) 844-5396    Victoria.rodriquez@uhhospitals.org   
Principal Investigator: Donald Hricik, MD         
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Jennifer Czerr    216-444-3256    czerrj@ccf.org   
Contact: Kimberly MacKay    216 444-4650    mackayk@ccf.org   
Principal Investigator: Emilio Poggio, MD         
United States, Texas
The Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Sarah Brann    713-441-6394    sjbrann@tmhs.org   
Principal Investigator: A. Osama Gaber, MD         
Canada, Manitoba
Health Sciences Centre Recruiting
Winnipeg, Manitoba, Canada, R3A IR9
Contact: Karin Janzen    (204) 787-8590    Kjanzen3@hsc.mb.ca   
Principal Investigator: David Rush, MD         
Principal Investigator: Peter Nickerson, MD         
Principal Investigator: Julie Ho, MD         
Canada, Ontario
Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M5G 2M1
Contact: Jill Sheedy    416-340-3125 ext 1    jill.sheedy@uhn.on.ca   
Contact: Heather Ford    416-340-4800 ext 2012    Heather.ford@uhn.on.ca   
Principal Investigator: Kathryn Tinckam, MD         
Sponsors and Collaborators
Investigators
Study Chair: Donald Hricik, MD University Hospital Case Medical Center
Principal Investigator: Peter S. Heeger, MD Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01517984     History of Changes
Other Study ID Numbers: DAIT CTOT-09
Study First Received: January 20, 2012
Last Updated: February 18, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Prednisone
Tacrolimus
Anti-Inflammatory Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014