Clinical trial NCT03586674: Fibrates in Pediatric Cholestasis
Official title: Fibrates: An Adjuvant Therapy for Cholestasis In Pediatric Age Group
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Cholestasis
Keywords: pediatric cholestasis, Fibrate
Lead sponsor: Ministry of Health and Population, Egypt
Sponsor class: OTHER_GOV
First posted: 2018-07-13
Enrollment: 50
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study conducted to assess the effect of fibrates on pruritus and biochemical picture in pediatric patients with cholestatic liver diseases.

Detailed description: Cholestatic liver disorders include a spectrum of hepatobiliary diseases of diverse etiologies that are characterized by impaired hepatocellular secretion of bile, resulting in accumulation of bile acids, bilirubin and cholesterol.This could result in different clinical features including pruritus, malabsorption and vitamin deficiencies with subsequent coagulation disorders and bone disease. Persistence of cholestasis leads to biliary fibrosis which can progress to liver cirrhosis and end-stage liver disease.

Nuclear receptors (NRs) regulate ligand-activated transcription factor networks of genes for the elimination and detoxification of potentially toxic biliary constituents accumulating in cholestasis. Activation of several NRs also modulates fibrogenesis, inflammation, and carcinogenesis as sequelae of cholestasis. Hence, It represent attractive targets for pharmacotherapy of cholestatic disorders.

Several already available drugs may exert their beneficial effects in cholestasis via NR activation eg, ursodeoxycholic acid via glucocorticoid receptor and pregnane X receptor, and rifampicin via pregnane X receptor. Unfortunately, Some patients may not respond to these medications.

Fibrates, serum Lipid lowering medication, has a stimulation action on proliferator activated receptor alpha. It is a nuclear receptor with an integral role in bile homeostasis. Several case reports and pilot studies have demonstrated the efficacy of fibrates in reducing serum biomarkers of cholestasis and liver function abnormalities in patients with incomplete response to ursodeoxycholic acid monotherapy. These results are of interest, because fibrates are attracting increased attention as adjunct therapy for chronic cholestatic liver diseases.

Eligibility criteria: Inclusion Criteria:

* Patient with chronic cholestatic liver disease defined as any condition in which substances normally excreted into bile are retained for more than 6 months.

Exclusion Criteria:

* Patients with anatomical or mechanical obstructive causes for cholestasis.
* Cholestatic patients who were suffering from another liver disease.
* Cholestatic patients who were receiving drugs affecting lipid profile.
* Patients receiving drugs that interact with Fenofibrate (FF) e.g statins and warfarin
* Patients with non obstructive gall bladder stones were excluded from T gp.

Primary outcomes:
measure: Change in the pruritus grading score
timeFrame: four months
Secondary outcomes:
measure: Changes in the liver function test and lipid profile
timeFrame: four months
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Dr. Yassin Abdel Ghaffar Charity Center For Liver Diseases & Researches
state: Nasr City
city: Shibīn Al Kawm
country: Egypt
facility: National liver istitute
Study officials:
affiliation: ASU
name: Tawhida Y Abdel Ghaffar, MD
role: STUDY_DIRECTOR
References:
citation: Ghonem NS, Boyer JL. Fibrates as adjuvant therapy for chronic cholestatic liver disease: its time has come. Hepatology. 2013 May;57(5):1691-3. doi: 10.1002/hep.26155. Epub 2013 Apr 5. No abstract available.