Mechanisms and Treatment of Chronic Allograft Injury (CAI) Due to Calcineurin Inhibitor (CNI) Toxicity
|ClinicalTrials.gov Identifier: NCT01473732|
Recruitment Status : Unknown
Verified November 2011 by Montefiore Medical Center.
Recruitment status was: Active, not recruiting
First Posted : November 17, 2011
Last Update Posted : November 17, 2011
|Condition or disease||Intervention/treatment||Phase|
|Chronic Allograft Injury Calcineurin Inhibitor Toxicity||Drug: Everolimus Drug: Tacrolimus||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Mechanisms and Treatment of Chronic Allograft Injury (CAI) Due to Calcineurin Inhibitor (CNI) Toxicity|
|Study Start Date :||November 2011|
|Estimated Primary Completion Date :||December 2013|
|Experimental: Everolimus (Zortress)+ Mycophenolic acid(Myfortic)||
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)||
Target trough level of Tacrolimus 3-5 ng/ml. Myfortic Min. 360 mg bid and Max. 720 mg bid Both for one year.
- EFFICACY AND SAFETY ASSESMENT [ Time Frame: One year ]
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:
- Acute rejection rate > 30%
- Serious infection rate > 50%
- > 50% progression of kidney dysfunction in one third of patients by eGFR
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01473732
|United States, New York|
|Montefiore Medical Center|
|Bronx, New York, United States, 10467|
|Principal Investigator:||Enver Akalin, MD||Montefiore Medical Center/AECOM|