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The Vienna Prograf and Endothelial Progenitor Cell Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gere Sunder-Plassmann, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT00182559
First received: September 10, 2005
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

The aim of the study is to determine if the conversion from the immunosuppressive agent cyclosporine to tacrolimus contributes to an improvement of the cardiovascular risk factors, better kidney function and immune system.


Condition Intervention Phase
End Stage Renal Disease
Drug: Ciclosporin
Drug: Tacrolimus
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: The Vienna Prograf and Endothelial Progenitor Cell Study

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Change in endothelial progenitor cells from baseline to month 24 [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
    The primary endpoint was the effect of conversion from ciclosporin to tacrolimus based immunosuppressive therapy on endothelial progenitor cell count at month 24.


Secondary Outcome Measures:
  • Renal function at baseline and after 24 months [ Time Frame: Baseline, 24 months ] [ Designated as safety issue: Yes ]
    Changes in risk factors for cardiovascular outcomes like serum lipids, blood pressure, diabetes mellitus, serum C-reactive protein, body mass index. Safety was addressed according to the incidence of medical necessity to change immunosuppressive therapy, serious opportunistic infection, new-onset diabetes mellitus, cardiovascular events, malignancy, lymphoma and lymphoproliferative disease, gingival hyperplasia, hypertrichosis, alopecia, graft loss and death.


Enrollment: 148
Study Start Date: April 2004
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ciclosporin
Maintain ciclosporin in combination with/without mycophenolate mofetil and with/without steroids at target trough levels of 70-150ng/mL.
Drug: Ciclosporin
Maintain ciclosporin in combination with/without mycophenolate mofetil and with/without steroids at target trough levels of 70-150ng/mL.
Other Name: Sandimmun Neoral
Active Comparator: Tacrolimus
Conversion from ciclosporin to tacrolimus at target trough levels of 5-8 ng/mL in combination with/without mycophenolate mofetil and with/without steroids.
Drug: Tacrolimus
Conversion from ciclosporin to tacrolimus at target trough levels of 5-8 ng/mL in combination with/without mycophenolate mofetil and with/without steroids.
Other Name: Prograf

Detailed Description:

In addition to hypertension, diabetes, hyperlipidemia and smoking, as well as other non-traditional risk factors such as elevated C-reactive protein, homocysteine, Lp(a), or reduced renal function, depletion of endothelial progenitor cells (EPC) in the peripheral circulation may represent another important explanation for the excess cardiovascular morbidity of kidney transplant recipients. In this context, the potential association of immunosuppressive therapy with EPCs in kidney transplant recipients deserves special consideration. The use of tacrolimus associated with a more favorable cardiovascular risk factors profile in terms of improved blood pressure and lipid levels in kidney transplant recipients compared to cyclosporine users. Therefore, one can speculate whether tacrolimus users might have greater EPC counts compared to patients treated with cyclosporine.

In a pilot study we cross-sectionally studied EPC counts in 90 stable, middle-aged kidney transplant recipients. From multivariate analyses, we found a independent inverse association between EPC counts and body mass index and systolic blood pressure. Statin use was associated with greater EPC counts, while patients receiving azathioprine had lower EPC counts. These findings raised the hypothesis whether EPCs are responsible, at least in part, for the well-established association between these factors and cardiovascular outcomes.

Cystatin C is superior to serum creatinine as a marker of kidney function since cystatin C is a more sensitive marker than serum creatine for small changes in glomerular filtration rate. Until now, there are no available data on the change of cystatin C as a measure of graft function after conversion of a cyclosporine based immunosuppressive regimen to tacrolimus.

There is accumulating evidence for an important pathogenetic role of donor-reactive antibodies in kidney allograft rejection. Recent studies suggest an anti-humoral activity of tacrolimus in the setting of chronic rejection. Recent findings suggest that in patients who are on cyclosporine, tacrolimus rescue therapy could efficiently inhibit antibody formation.

Objective 1: To evaluate the change in endothelial progenitor cell (EPC) count in kidney graft recipients converted from cyclosporine to tacrolimus.

Objective 2: To evaluate the change in cystatin C as a measure of renal function in kidney graft recipients converted from cyclosporine to tacrolimus.

Objective 3: To determine the effect of tacrolimus on humoral alloreactivity in kidney graft recipients Study design: A 2:1 randomized, parallel group, open-label, prospective trial comparing two different immunosuppressive regimens in approximately 148 patients. Group A: Convert to tacrolimus in combination with/without mycophenolate mofetil and/or steroids. Group B: Maintain cyclosporine in combination with/without mycophenolate mofetil and/or steroids. Patients will be followed up for 24 months after conversion.

In an amendment (August 2006) we registered pharmacogenetic analyses of the multi-drug resistance transporter 1 (MDR1) gene (gene symbol: ABCB1). The patients´ DNA is extracted from peripheral venous blood manually with industrial extraction kits. Two gene sections are amplified by polymerase chain reaction (PCR). Mutations are determined by restriction enzymes (restriction fragment length polymorphisms, RFLP).

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient is recipient of a deceased or living donor renal transplant (including retransplants) Patient is 18 years or age or older at the time of transplantation. Patient is at least 6 months post-transplant. Patient is on a cyclosporine-based immunosuppression regimen o combination with/without mycophenolate mofetil and/or steroids at study entry.

Patient has a functioning renal allograft and estimated GFR≥39 mL/min/1.73m2 within four weeks prior to study entry.

Patient has a stable graft function without biopsy proven acute rejection episode within 3 months prior to study entry.

Patient has not experienced a cardiovascular event. Patient has fully been informed and has given written informed consent according to the International Conference on Harmonization, Good Clinical Practice.

Females are not pregnant and agree to practice effective birth control while receiving immunosuppressant medication.

Patient has indications for conversion at the investigators discretion or is suffering from cyclosporine associated side effects like hypertension, hyperlipidemia or cosmetic side effects.

Exclusion Criteria:

  • Patient is recipient of a solid organ transplant other than the kidney. Patient has recurrence of primary renal disease, or de novo renal disease. Patient is pregnant or lactating. Patient had known or suspected malignancy (except for treated squamous and basal cell skin cancers) <5 years before study entry or a history of post-transplant lymphoproliferative disease (PTLD).

Patient has known hypersensitivity to tacrolimus, or any of the recipients of the drug.

  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: NCT00182559

Locations
Austria
Medical University of Vienna
Vienna, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Gere Sunder-Plassmann, M.D. Medical University of Vienna
  More Information

Additional Information:
No publications provided by Medical University of Vienna

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gere Sunder-Plassmann, Principal Investigator Prof. Dr., Medical University of Vienna
ClinicalTrials.gov Identifier: NCT00182559     History of Changes
Other Study ID Numbers: 2004-004209-98, 393/2004
Study First Received: September 10, 2005
Last Updated: February 4, 2014
Health Authority: Austria: Federal Ministry for Health and Women

Keywords provided by Medical University of Vienna:
kidney
transplantation
tacrolimus
cyclosporine
conversion

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Renal Insufficiency
Renal Insufficiency, Chronic
Urologic Diseases
Cyclosporine
Cyclosporins
Mycophenolate mofetil
Mycophenolic Acid
Tacrolimus
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014