Clinical trial NCT05021159: Assessing the Ontogeny of P-glycoprotein Expression in Blood of Pediatric Leukemic Patients
Official title: Assessing the Ontogeny of P-glycoprotein Expression in Blood of Pediatric Leukemic Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Lymphocytic Leukemia
Lead sponsor: Tanta University
Sponsor class: OTHER
First posted: 2021-08-25
Enrollment: 20
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Pediatric Acute Lymphocytic Leukemia Patients aged \< 18 years old who are already taking the ALL MTX protocol.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: P-gp expression in blood samples
timeFrame: 42 hours
measure: Methotrexate concentration in blood samples
timeFrame: 42 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Tanta
country: Egypt
facility: Faculty of Pharmacy, Tanta University
state: Gharbiya
city: Tanta
country: Egypt
facility: Tanta Cancer Center
state: Gharbiya
city: Tanta
country: Egypt
facility: Tanta University
state: Gharbiya
Study officials:
affiliation: Assistant lecturer in Clinical Pharmacy Dept., Faculty of pahrmacy, Tanta University
name: Yasmine M Elmorsi, Msc
role: PRINCIPAL_INVESTIGATOR
affiliation: Professor in Clinical Pharmacy Dept., Faculty of pahrmacy, Tanta University
name: Osama M Ibrahim, Professor
role: STUDY_CHAIR
affiliation: Assistant Professor in Clinical Pharmacy Dept., Faculty of pahrmacy, Tanta University
name: Tarek M Mostafa, Professor
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.