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

NCT ID: NCT03830255

Last Updated: 2021-03-30

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 143 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-03-01
• Study Completion Date: 2020-03-29

Brief Summary

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.

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

Conditions

Renal Transplantation

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Renal Transplant patients treated with cyclosporine

Detecting the genetic polymorphism affecting cyclosporine level

No interventions assigned to this group

Renal Transplant patients treated with tacrolimus

Detecting the genetic polymorphism affecting tacrolimus level

No interventions assigned to this group

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ain Shams University

OTHER

Sponsor Role: collaborator

Helwan University

OTHER

Sponsor Role: lead

Responsible Party

Dina Ahmed Mohamed Ali Ismail

Lecturer Assistant at Clinical Pharmacy and Pharmacy Practice department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Magdy El Sharkawy, MD

Role: PRINCIPAL_INVESTIGATOR

Ain Shams University

Abdel hameed Ibrahim Mohamed Ebid, PhD

Role: STUDY_DIRECTOR

Helwan University

Neama Lotfy, MD

Role: STUDY_DIRECTOR

Ain sham university

Mohamed Adel, PhD

Role: STUDY_DIRECTOR

Helwan University

Locations

Ain shams university specialized hospital

Cairo, , Egypt

Countries

Egypt

Other Identifiers

FWA000017585

Identifier Type: -

Identifier Source: org_study_id