The Effects of Conversion From Cyclosporine to Tacrolimus on the Changes of Cardiovascular Risk Profiles and Serum Metabolites in Renal Transplant Recipients

The purpose of this study is to evaluate the effects of conversion from cyclosporine to tacrolimus on the changes of cardiovascular risk profiles and serum metabolites in renal transplant recipients.

Study Overview

• Status: Unknown
• Conditions: CYCLOSPORINE/TACROLIMUS
• Intervention / Treatment: Drug: Tacrolimus

Detailed Description

During the past two decades, cyclosporine has proved to be a valuable immunosuppressive drug that has contributed to a significant reduction in the incidence of acute rejection after kidney transplantation. However, cyclosporine is known as a major factor causing cardiovascular death in kidney transplant recipients. Moreover, cyclosporine has an adverse effect on the lipid profile and fibrinolytic system and result in hypertension and cardiovascular disease. Immunosupressive mechanism of tacrolimus is identical that of cyclosporine but it is 100 times more potent T cell inhibitor than cyclosporine. In multicenter study of Europe and United states, tacrolimus showed low incidence of acute rejection and was known to effective in acute rejection resistant to other therapy. Tacrolimus has a lot of advantages compared to cyclosporine in terms of hypertensive and hyperlipidemic effects although evidences are lacking. One study demonstrated cardiovascular risk profile and renal function has been improved in kidney transplant patients after randomized conversion from cyclosporine to tacrolimus Previous study analyzing metabolites of tacrolimus and cyclosporine revealed that differences were observed in the metabolite level of hypoxanthine, lactate, succinate, and taurine between two immunosupressants. The objective of this study is to evaluate changes in cardiovascular risk profiles and metabolite patterns after conversion from cyclosporine to tacrolimus in kidney transplant recipients.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of
    • Recruiting
    • Kyungpook National University Hospital
    • Contact: Chan-Duck Kim; Email: drcdkim@knu.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients who received a kidney transplant at least 12 months ago prior to enrollment
2. Patients who have kept in unchanged cyclosporine therapy at least for 6 months prior to enrollment.
3. Female patients of childbearing potential must have a negative urine or serum pregnancy test prior to enrollment, and agreed to the deliberate prevention of conception during the trial
4. Patients who are considered clinically stable by observer's judgment.
5. Patients must understand the purpose and risk of participating the the trial and signed on the written consent.

Exclusion Criteria:

1. Patients who have previously received an organ transplant other than a kidney
2. Patients diagnosed with congestive heart failure within 6 months (EF <35%)
3. Patients with untreated ischemic heart disease
4. Patients whose hemoglobin is in the level of <7.0 g/dL
5. Patients who have a known hypersensitivity to tacrolimus
6. Patients taking potassium sparing diuretics
7. Patients newly diagnosed malignant tumors after organ transplant but the patients treated completely with basal or squamous cell carcinoma of the skin are excepted
8. Patients who are at the risk of drug abuse or mental disorders or communicate difficulties with the observer
9. Patients who are pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tacrolimus conversion group; Cyclosprine was converted to tacrolimus in kidney transplant recipients.	Drug: Tacrolimus; Tacrolimus for maintenance immunosupression in kidney transplant recipients; Other Names: TacroBell

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Blood Pressure at 6 months	3 months, 6 months
Change from Baseline in Lipid Profile at 6 months	3 months, 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Assessing glucose regulation using blood glucose and hemoglobin A1c	3 months, 6 months
Assessing other metabolic cardiovascular risk factors using fibrinogen, tPA, PAI-I, homocysteine, pro-BNP, hs-CRP, uric acid	24 weeks
Assessing serum metabolite using ELISA	3 months, 6 months
Assessing renal function using blood urea nitrogen and creatinine	3 months, 6 months

Collaborators and Investigators

• Sponsor: Kyungpook National University Hospital
• Investigators: Principal Investigator: Chan-Duck Kim, Kyungpook National University Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Anticipated): July 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: July 3, 2015
• First Submitted That Met QC Criteria: July 13, 2015
• First Posted (Estimate): July 14, 2015

Study Record Updates

• Last Update Posted (Estimate): July 14, 2015
• Last Update Submitted That Met QC Criteria: July 13, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: KNUH 2012-09-010