Mechanisms and Treatment of Chronic Allograft Injury (CAI) Due to Calcineurin Inhibitor (CNI) Toxicity

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2011 by Montefiore Medical Center.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
Montefiore Medical Center
ClinicalTrials.gov Identifier:
NCT01473732
First received: November 14, 2011
Last updated: November 16, 2011
Last verified: November 2011
  Purpose

The purpose of this study is to find out how well the current drug regimen (including low Prograf dose and Myfortic, which is usually recommended to prevent any further deterioration in the kidney function) works and how safe it is when compared to a combination of Zortress and Myfortic in patients with chronic kidney injury associated with Prograf or Neoral use.


Condition Intervention
Chronic Allograft Injury
Calcineurin Inhibitor Toxicity
Drug: Everolimus
Drug: Tacrolimus

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Mechanisms and Treatment of Chronic Allograft Injury (CAI) Due to Calcineurin Inhibitor (CNI) Toxicity

Resource links provided by NLM:


Further study details as provided by Montefiore Medical Center:

Primary Outcome Measures:
  • EFFICACY AND SAFETY ASSESMENT [ Time Frame: One year ] [ Designated as safety issue: Yes ]

    Patients will be evaluated in terms of acute rejection episodes, graft loss, death, infection episodes, malignancies and graft function at each clinic visit.

    Study will be terminated in these circumstances:

    1. Acute rejection rate > 30%
    2. Serious infection rate > 50%
    3. > 50% progression of kidney dysfunction in one third of patients by eGFR


Estimated Enrollment: 30
Study Start Date: November 2011
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus (Zortress)+ Mycophenolic acid(Myfortic) Drug: Everolimus
Starting dose 1.5 mg bid, target trough level 6-10 ng/ml. Myfortic Min. dose 360 mg bid and Max dose 720 mg bid. Both for one year.
Active Comparator: Reduced dose Prograf+ Mycophenolic acid(Myfortic) Drug: Tacrolimus
Target trough level of Tacrolimus 3-5 ng/ml. Myfortic Min. 360 mg bid and Max. 720 mg bid Both for one year.

Detailed Description:

Specific Aim 1: To investigate allograft and peripheral blood cell gene expression patterns of patients with CAI by using Affymetrix microarrays.

Hypothesis 1: Gene expression patterns of patients with biopsy findings suggesting calcineurin inhibitor (CNI) toxicity without significant tubulointerstitial infiltrates or transplant glomerulopathy might demonstrate upregulation of genes related to tissue injury, fibrosis, and extracellular matrix deposition without upregulation of genes related to alloimmune response, such as, T and/or B lymphocyte activation markers, surface receptors, co-stimulation molecules, adhesion molecules, cytokines, and chemokines comparing to patients with significant tubulointerstitial infiltrates and/or transplant glomerulopathy that might show upregulation of genes related to alloimmune response, such as, T and/or B lymphocyte activation markers, surface receptors, co-stimulation molecules, adhesion molecules, cytokines, and chemokines.

Specific Aim 2: The effect of everolimus (Zortress)/ mycophenolate sodium (EC-MPS, myfortic®) treatment on allograft and peripheral gene expression patterns.

Hypothesis 2: Everolimus (Zortress) and mycophenolate sodium (EC-MPS, myfortic®) treatment attenuates the progression of CAI due to CNI toxicity by downregulating the expression of genes related to fibrosis, such as, transforming growth factor-β, thrombospondin 1, and platelet derived growth factor-C.

Specific Aim 3: To document the clinical outcomes of everolimus (Zortress) and mycophenolate sodium (EC-MPS, myfortic®) in patients with CAI due to CNI toxicity Hypothesis 3: Everolimus (Zortress) and mycophenolate sodium (EC-MPS, myfortic®) can attenuate the progression of CAI due to CNI toxicity and may improve the creatinine clearance.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All patients with biopsy proven pure chronic allograft injury due to CNI toxicity.

Exclusion Criteria:

  1. 24 hour urine protein or spot urine protein/creatinine ratio > 500 mg/day
  2. eGFR < 30 ml/min by MDRD or 24 hour urine collection
  3. Patients with DSAs by Luminex (mean fluorescence intensity values > 1,000)
  4. Recipients of multiple organ transplants or ABO-incompatible allograft
  5. Current PRA greater than 30 percent
  6. Graft loss at randomization
  7. Pregnant women
  8. Previous history of acute rejection
  9. Previous history of allergy or intolerance to Zortress or Myfortic
  10. Platelet count less than 100,000
  11. WBC less than 3,000
  12. Hb less than 9 g/dL or Htc less than 30%
  13. Biopsy findings of

    • Chronic antibody mediated rejection
    • Acute rejection
    • Positive C4d staining
    • Interstitial infiltrates more than 25% of the area
    • Transplant glomerulopathy
    • Recurrent or de novo glomerular disease
    • Polyoma nephropathy or positive SV40 staining
  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: NCT01473732

Locations
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
Sponsors and Collaborators
Montefiore Medical Center
Investigators
Principal Investigator: Enver Akalin, MD Montefiore Medical Center/AECOM
  More Information

No publications provided

Responsible Party: Montefiore Medical Center
ClinicalTrials.gov Identifier: NCT01473732     History of Changes
Other Study ID Numbers: 11-05-196
Study First Received: November 14, 2011
Last Updated: November 16, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Montefiore Medical Center:
CNI toxicity
CAI

Additional relevant MeSH terms:
Wounds and Injuries
Everolimus
Sirolimus
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on August 28, 2014