NCT01473732

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

• Status: Terminated
• Phase: N/A
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Montefiore Medical Center · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• Chronic Allograft Injury
• Calcineurin Inhibitor Toxicity

Interventions

Type	Name	Description
DRUG	Everolimus	Starting dose 1.5 mg bid, target trough level 6-10 ng/ml.
DRUG	Tacrolimus	Target trough level of Tacrolimus 3-5 ng/ml.
DRUG	Mycophenolic acid	Myfortic Min. dose 360 mg bid and Max dose 720 mg bid. Used in both arms. Used for one year.

Timeline

• Start date: 2012-03-01
• Primary completion: 2012-08-01
• Completion: 2012-08-01
• First posted: 2011-11-17
• Last updated: 2018-10-16
• Results posted: 2018-09-18

Locations

1 site across 1 country: United States