Clinical trial NCT02602873: Study of Tacrolimus Used for Pediatric Patients With Nephrotic Syndrome Based on Pharmacogenomics and Metabonomics
Official title: Guangzhou Women and Children's Medical Center
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Nephrotic Syndrome
Lead sponsor: Guangzhou Women and Children's Medical Center
Sponsor class: OTHER
Collaborators: name: Sun Yat-sen University
First posted: 2015-11-11
Enrollment: 150
Sex: ALL
Minimum age (years): 1
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Sampling method: NON_PROBABILITY_SAMPLE
Study population: pediatric patients with nephrotic syndrome

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.

Detailed description: Investigators will collect data about efficacy and adverse drug reaction(ADR) such as time of efficacy when evaluated, how to evaluate ADR, data of demography, etc.

Eligibility criteria: Inclusion Criteria:

1. patients with refractory nephrotic syndrome;
2. patients age ≤14y.

Exclusion Criteria:

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

Primary outcomes:
measure: "Genotypes as measured by polymerase chain reaction-restriction fragment length polymorphism"
timeFrame: 1 week
measure: "Concentration as measured by liquid chromatography mass spectrometry"
timeFrame: 1 week
measure: "Relationship between genotypes and concentration as analyzed at 1 week"
timeFrame: 1 week
Secondary outcomes:
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangzhou women and children's medical center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Min Huang, Doctor
role: STUDY_DIRECTOR
References:
citation: 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.