Clinical trial NCT03830255: Effect of Genetic Polymorphism on Calcineurin Inhibitors Levels in Egyptian Renal Transplant Patients
Official title: Calcineurin Inhibitors Among Egyptian Renal Transplant Patients: a Pharmacognetic Based Study.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Renal Transplantation
Keywords: Renal Transplantation
Genetic Polymorphism
CYP3A5
CYP3A4
Lead sponsor: Helwan University
Sponsor class: OTHER
Collaborators: name: Ain Shams University
First posted: 2019-02-05
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Renal Transplant Patients

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

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

Primary outcomes:
measure: CYP enzymes genetic polymorphism and calcineurin inhibitors drug levels
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain shams university specialized hospital
Study officials:
affiliation: Ain Shams University
name: Magdy El Sharkawy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Helwan University
name: Abdel hameed Ibrahim Mohamed Ebid, PhD
role: STUDY_DIRECTOR
affiliation: Ain sham university
name: Neama Lotfy, MD
role: STUDY_DIRECTOR
affiliation: Helwan University
name: Mohamed Adel, PhD
role: STUDY_DIRECTOR
References: