Study of Tacrolimus Used for Pediatric Patients With Nephrotic Syndrome Based on Pharmacogenomics and Metabonomics

NCT02602873 | Unknown

• 1 other identifier: 683292136
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Tacrolimus is recommended to be the first line therapeutic medication within the several immunosuppressive agents when treating refractory pediatric nephrotic syndrome, because of its definite efficacy and low toxicity. But there are still some key problems which hinder the using of tacrolimus in clinic, such as its narrow therapeutic widow, great individual difference of pharmacokinetics. Routine therapeutic drug monitoring(TDM) is needed in practice. But the disadvantage of TDM is hysteresis, which could lead to treatment failure or toxicity. To find out the reasons of great pharmacokinetic difference between patients and find out the individual proper dosage before administration are important for the clinical using of tacrolimus. It is hot in research of tacrolimus in organ transplant field, such as the association between gene polymorphisms of cytochrome P-450 3A4, 3A5 and multiple drug resistant gene(MDR1) and concentration of tacrolimus. However, there is few study about pharmacogenomics and metabonomics of tacrolimus in patients of nephrotic syndrome. The aim is to study the relationships between pharmacogenomics, metabonomics of tacrolimus and its efficacy, toxicity and blood concentration in patients of nephrotic syndrome, to find out the exact dosage before administration, to provide reference to individual drug administration.

Conditions

Nephrotic Syndrome

Outcome Measures

Primary Outcomes (3)

• "Genotypes as measured by polymerase chain reaction-restriction fragment length polymorphism"

  genotype are collected from hospital system.

  1 week

• "Concentration as measured by liquid chromatography mass spectrometry"

  concentration of tacrolimus are collected from hospital system.

  1 week

• "Relationship between genotypes and concentration as analyzed at 1 week"

  using Statistic Package for Social Science 21.0 software to analyze the relationship between gene polymorphism and concentration.

  1 week

Study Arms (2)

good efficacy

using therapeutic drug monitoring to adjust the dose of tacrolimus. patients can reach effective outcome.

Other: therapeutic drug monitoring

poor efficacy

using therapeutic drug monitoring to adjust the dose of tacrolimus. patients can not reach effective outcome.

Other: therapeutic drug monitoring

Interventions

therapeutic drug monitoring OTHER

with therapeutic drug monitoring , dose of tacrolimus can be adjusted by therapeutic drug monitoring.

good efficacy; poor efficacy

Eligibility Criteria

• Age: 1 Month - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

pediatric patients with nephrotic syndrome

You may qualify if:

• patients with refractory nephrotic syndrome;
• patients age ≤14y.

You may not qualify if:

• patients are sensitive to steroid;
• combined therapy with other immunosuppressive agent;
• combined using drugs which maybe interact the concentration of tacrolimus;
• with other malignant disease, such as tumor.

Sponsors & Collaborators

• Guangzhou Women and Children's Medical Center: lead
• Sun Yat-sen University: collaborator

Study Sites (1)

Guangzhou women and children's medical center

Guangzhou, Guangdong, 510623, China

Location

Related Publications (1)

• Mo X, Li J, Liu Y, Liao X, Tan M, Chen Y, He F, He Y, Li Y, Huang M. Kidney podocyte-associated gene polymorphisms affect tacrolimus concentration in pediatric patients with refractory nephrotic syndrome. Pharmacogenomics J. 2020 Aug;20(4):543-552. doi: 10.1038/s41397-019-0141-x. Epub 2020 Jan 6.

  PMID: 31902946 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

DNAs extracted from whole blood are stored in freezer with -80 centigrade.

MeSH Terms

Conditions

Nephrotic Syndrome

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Min Huang, Doctor

  Sun Yat-sen University

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Pharmacist

Study Record Dates

• First Submitted: September 9, 2015
• First Posted: November 11, 2015
• Study Start: August 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: August 1, 2020
• Last Updated: August 12, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)