Effect of Genetic Polymorphism on Calcineurin Inhibitors Levels in Egyptian Renal Transplant Patients

Calcineurin Inhibitors Among Egyptian Renal Transplant Patients: a Pharmacognetic Based Study.

Renal transplantation is the treatment of choice for patients with end-stage renal disease (ESRD). Calcineurin Inhibitors tacrolimus and cyclosporine are the principle immunosuppressive agents administered to solid organ transplant recipients to prevent and treat allograft rejection.

The aim of the present study is to detect the incidence of some selected genetic polymorphism in Egyptian renal transplant population and investigate the influence of these genetic polymorphism (SNPs )on Cyclosporine and Tacrolimus blood concentration. In addition to detect the association between these genetic polymorphism variants and patients' clinical outcome after transplantation.

Study Overview

• Status: Completed
• Conditions: Renal Transplantation

Detailed Description

Tacrolimus and cyclosporine are the principle immunosuppressive agents administered to solid organ transplant recipients to prevent and treat allograft rejection.They both exert their immunosppressive action by inhibiting the calcinurein in T-lymphoctes. Subsequently,Cyclosporin and tacrolimus are both metabolic substrates for cytochrome P450 (CYP) 3A enzymes - in particular, CYP3A4 and CYP3A5 - and are transported out of cells by the P-glycoprotein (ABCB1) efflux pump. Different expression of CYP3A4, CYP3A5 and P-glycoprotein causes patient to-patient variability in the absorption, metabolism and tissue distribution of calcineurin inhibitors. This different expression is likely to be at least partially the result of mutations in the genes encoding for these enzymes and drug transporter. This may lead to variable drug concentrations within the systemic circulation and at target sites, influencing drug efficacy. Moreover, it will influence the individual's susceptibility to drug interactions and drug toxicity

• Study Type: Observational
• Enrollment (Actual): 143

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Ain Shams University Specialized Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Renal Transplant Patients

Description

Inclusion Criteria:

1. Kidney transplant patients.
2. Treatment with calcineurin inhibitors (CNI) either Cyclosporine (Neoral®) or Tacrolimus (Prograf®).
3. Absence of medication known to interact with CNI
4. Age18 years and more

Exclusion Criteria:

1. Patient who experience acute rejection, graft failure.
2. Medications that interact with Calcineurin Inhibitors.
3. Pregnant or nursing women.
4. Patients who decline to participate

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Renal Transplant patients treated with cyclosporine; Detecting the genetic polymorphism affecting cyclosporine level
Renal Transplant patients treated with tacrolimus; Detecting the genetic polymorphism affecting tacrolimus level

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CYP enzymes genetic polymorphism and calcineurin inhibitors drug levels	Association of CP3A4 and CYP3A5 genetic polymorphism SNPs on Cyclosporine and Tacrolimus blood concentration	3 months

Collaborators and Investigators

• Sponsor: Helwan University
• Collaborators: Ain Shams University
• Investigators: Principal Investigator: Magdy El Sharkawy, MD, Ain Shams University; Study Director: Abdel hameed Ibrahim Mohamed Ebid, PhD, Helwan University; Study Director: Neama Lotfy, MD, Ain sham university; Study Director: Mohamed Adel, PhD, Helwan University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): October 1, 2019
• Study Completion (Actual): March 29, 2020

Study Registration Dates

• First Submitted: February 1, 2019
• First Submitted That Met QC Criteria: February 1, 2019
• First Posted (Actual): February 5, 2019

Study Record Updates

• Last Update Posted (Actual): March 30, 2021
• Last Update Submitted That Met QC Criteria: March 25, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Renal Transplantation; Genetic Polymorphism; CYP3A4; CYP3A5
• Other Study ID Numbers: FWA000017585

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No