Chronic Allograft InjuryNCT01473732
Mechanisms and Treatment of Chronic Allograft Injury (CAI) Due to Calcineurin Inhibitor (CNI) Toxicity
A study testing Everolimus, Tacrolimus and Mycophenolic acid in people with Chronic Allograft Injury and Calcineurin Inhibitor Toxicity, run by Montefiore Medical Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Chronic Allograft Injury, Calcineurin Inhibitor Toxicity
- What is being tested?
- Everolimus, Tacrolimus and Mycophenolic acid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to Aug 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All patients with biopsy proven pure chronic allograft injury due to CNI toxicity.
Who cannot join
- 24 hour urine protein or spot urine protein/creatinine ratio > 500 mg/day
- Estimated glomerular filtration rate (eGFR) < 30 ml/min by modification of Diet in Renal Disease( MDRD) or 24 hour urine collection
- Patients with Donor-specific antibody (DSA) by Luminex (mean fluorescence intensity values > 1,000)
- Recipients of multiple organ transplants or ABO-incompatible allograft
- Current panel reactive antibody (PRA) greater than 30 percent
- Graft loss at randomization
Show all 20Show fewer
- Pregnant women
- Previous history of acute rejection
- Previous history of allergy or intolerance to Zortress or Myfortic
- Platelet count less than 100,000
- White Blood Cell (WBC) less than 3,000
- Hb less than 9 g/dL or Htc less than 30%
- 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 simian virus 40 (SV40) staining
Trial locations and contacts
1 site in 1 country.
United States1 site
Montefiore Medical Center
The Bronx, New York, 10467
About this study
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.
Read the 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.
- Being tested
- Everolimus, Tacrolimus, Mycophenolic acid
- Keywords
- CNI toxicity, CAI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called Zortress
Starting dose 1.5 mg bid, target trough level 6-10 ng/ml.
TacrolimusDrug
Also called Prograf
Target trough level of Tacrolimus 3-5 ng/ml.
Mycophenolic acidDrug
Also called Myfortic
Myfortic Min. dose 360 mg bid and Max dose 720 mg bid. Used in both arms. Used for one year.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus (Zortress) | Experimental | Not described Receives: Drug: Everolimus; Drug: Mycophenolic acid |
| Reduced dose Tacrolimus (Prograf) | Active comparator | Not described Receives: Drug: Tacrolimus; Drug: Mycophenolic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in eGFR (Creatinine Clearance) as Measured by Serum Creatinine Blood Test
Estimated glomerular filtration rate (eGFR) indicates kidney function. Normal eGFR value for healthy is 80-120ml/min. For transplants, it is expected to be 60-80 ml/min.
Measured: Baseline, One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2011 (estimated)
- Study startMar 2012
- Primary completionAug 2012
- Study completionAug 2012
Why it stopped: terminated after 2 patients due to difficulty in enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Allograft InjuryStudies of the same condition, open and under way.
- More trials run by Montefiore Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Montefiore Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Enver Akalin, Montefiore Medical Center
- Investigators
- Enver Akalin, MD, Principal investigator, Montefiore Medical Center/AECOM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01473732
- Sponsor's protocol ID
- 11-05-196
- Status last verified
- Sep 2018
- First submitted
- 14 Nov 2011
- Last updated
- 16 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms and Treatment of Chronic Allograft Injury (CAI) Due to Calcineurin Inhibitor (CNI) Toxicity
- ClinicalTrials.gov ID
- NCT01473732
- Acronym / sponsor ID
- 11-05-196
- Keywords
- CNI toxicity, CAI
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: terminated after 2 patients due to difficulty in enrollment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Montefiore Medical CenterUniversity, hospital or other
- Study start
- Mar 2012 (actual)
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 17 Nov 2011 (estimated)
- Results
- Posted 18 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus (Zortress) | Experimental | Drug: Everolimus, Drug: Mycophenolic acid |
| Reduced dose Tacrolimus (Prograf) | Active comparator | Drug: Tacrolimus, Drug: Mycophenolic acid |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- All patients with biopsy proven pure chronic allograft injury due to CNI toxicity.
Key exclusion criteria (20 listed)
- 24 hour urine protein or spot urine protein/creatinine ratio > 500 mg/day
- Estimated glomerular filtration rate (eGFR) < 30 ml/min by modification of Diet in Renal Disease( MDRD) or 24 hour urine collection
- Patients with Donor-specific antibody (DSA) by Luminex (mean fluorescence intensity values > 1,000)
- Recipients of multiple organ transplants or ABO-incompatible allograft
- Current panel reactive antibody (PRA) greater than 30 percent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusAlso: ZortressStarting dose 1.5 mg bid, target trough level 6-10 ng/ml. | Drug | Everolimus (Zortress) |
| TacrolimusAlso: PrografTarget trough level of Tacrolimus 3-5 ng/ml. | Drug | Reduced dose Tacrolimus (Prograf) |
| Mycophenolic acidAlso: MyforticMyfortic Min. dose 360 mg bid and Max dose 720 mg bid. Used in both arms. Used for one year. | Drug | Everolimus (Zortress), Reduced dose Tacrolimus (Prograf) |
Primary outcome
Change in eGFR (Creatinine Clearance) as Measured by Serum Creatinine Blood Test
Time frame: Baseline, One year
Estimated glomerular filtration rate (eGFR) indicates kidney function. Normal eGFR value for healthy is 80-120ml/min. For transplants, it is expected to be 60-80 ml/min.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Enver Akalin, MD principal investigator
Montefiore Medical Center/AECOM
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Everolimus, Tacrolimus and Mycophenolic acid in people with Chronic Allograft Injury and Calcineurin Inhibitor Toxicity, run by Montefiore Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in eGFR (Creatinine Clearance) as Measured by Serum Creatinine Blood Test (time frame: Baseline, One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2018.