Assessing the Ontogeny of P-glycoprotein Expression in Blood of Pediatric Leukemic Patients

Determine P-glycoprotein expression in blood samples of Acute Lymphocytic leukemia (ALL) pediatric patients receiving MTX treatment and trace its ontogeny and compare it with its expression in pediatric healthy subjects. In addition, to determine the correlation of P-glycoprotein expression and Methotrexate concentration at steady state.

Study Overview

• Status: Completed
• Conditions: Acute Lymphocytic Leukemia
• Intervention / Treatment: Other: MTX, (but the investigator is not using any intervention, the participants are already taking it in their treatment protocol and the investigator is just analyzing p-gp expression)

Detailed Description

The 20 leukemic patients will be classified into three age groups according to the ages that will be available at the time of sample collection.

• All patients will be recruited from Tanta Oncology Center, Tanta University.
• The study will be approved by the Research Ethics Committee of Tanta University and college of Pharmacy ethical committee.
• An informed consent will be obtained from parents of all patients in this research before enrollment.
• All patients' data will be private and confidential. Any unexpected risks that may appear during the course of the research will be reported to patients and the ethical committee on time.

Blood Samples will be obtained from healthy pediatric subjects of the same ages of the diseased group subjects (Samples will be obtained from subjects from a primary care center during their routine blood analysis excluding patients of chronic diseases, patients receiving any medications, and patients of impaired kidney or liver functions).

P-glycoprotein expression will be estimated in all samples using Permeability glycoprotein (P-gp), ELISA Kit, and its expression will be traced with development from the youngest till the oldest age available, this will also be compared with normal healthy pediatric subjects.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Egypt
  • Gharbiya
    • Tanta, Gharbiya, Egypt, 31111
      • Faculty of Pharmacy, Tanta University
    • Tanta, Gharbiya, Egypt, 31111
      • Tanta Cancer Center
    • Tanta, Gharbiya, Egypt, 31111
      • Tanta University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Pediatric Acute Lymphocytic Leukemia Patients aged < 18 years old who are already taking the ALL MTX protocol.

Description

Inclusion Criteria:

• Pediatric Acute Lymphocytic Leukemia Patients
• aged < 18 years old
• who are already taking the ALL MTX protocol.

Exclusion Criteria:

• Severe renal impairment (eGFR< 30 mL/min/1.73 m2 at screening)

  • Critically ill patients.
  • Other types of cancer

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Methotrexate Group; 20 acute lymphocytic leukemia patients receiving MTX treatment (3- 5 mg/ cm2)	Other: MTX, (but the investigator is not using any intervention, the participants are already taking it in their treatment protocol and the investigator is just analyzing p-gp expression); the investigator is not using any intervention, the participants are already taking it in their treatment protocol and the investigator is just analyzing p-gp expression
Healthy control group; 20 healthy pediatric subjects not receiving any treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
P-gp expression in blood samples	P-gp expression in blood samples	42 hours
Methotrexate concentration in blood samples	Methotrexate concentration in blood samples	42 hours

Collaborators and Investigators

• Sponsor: Tanta University
• Investigators: Principal Investigator: Yasmine M Elmorsi, Msc, Assistant lecturer in Clinical Pharmacy Dept., Faculty of pahrmacy, Tanta University; Study Chair: Osama M Ibrahim, Professor, Professor in Clinical Pharmacy Dept., Faculty of pahrmacy, Tanta University; Study Chair: Tarek M Mostafa, Professor, Assistant Professor in Clinical Pharmacy Dept., Faculty of pahrmacy, Tanta University

Publications and helpful links

General Publications

• Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL, Chang G. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science. 2009 Mar 27;323(5922):1718-22. doi: 10.1126/science.1168750.
• Namanja HA, Emmert D, Davis DA, Campos C, Miller DS, Hrycyna CA, Chmielewski J. Toward eradicating HIV reservoirs in the brain: inhibiting P-glycoprotein at the blood-brain barrier with prodrug abacavir dimers. J Am Chem Soc. 2012 Feb 15;134(6):2976-80. doi: 10.1021/ja206867t. Epub 2011 Sep 9.
• Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology--drug disposition, action, and therapy in infants and children. N Engl J Med. 2003 Sep 18;349(12):1157-67. doi: 10.1056/NEJMra035092. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Actual): June 1, 2021
• Study Completion (Actual): August 1, 2021

Study Registration Dates

• First Submitted: August 19, 2021
• First Submitted That Met QC Criteria: August 24, 2021
• First Posted (Actual): August 25, 2021

Study Record Updates

• Last Update Posted (Actual): September 2, 2021
• Last Update Submitted That Met QC Criteria: August 28, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: 141052

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