Fibrates in Pediatric Cholestasis

Chronic Cholestasis Clinical Trial

Official title:

Fibrates: An Adjuvant Therapy for Cholestasis In Pediatric Age Group

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03586674
• Other study ID #: 1984
• Status: Completed
• Phase: Phase 2
• Start date: November 1, 2017
• Est. completion date: June 20, 2018

Study information

• Verified date: July 2018
• Source: Ministry of Health and Population, Egypt
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: June 20, 2018
• Est. primary completion date: June 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cholestasis
• Chronic Cholestasis

Intervention

Drug:
• Lipanthyl
Tablet
• Ursogal
suspension

Locations

Country	Name	City	State
Egypt	Dr. Yassin Abdel Ghaffar Charity Center For Liver Diseases & Researches	Cairo	Nasr City
Egypt	National liver istitute	Shibin Al Kawm

Sponsors (1)

Lead Sponsor	Collaborator
Hoda A. Atta

Country where clinical trial is conducted

Egypt, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the pruritus grading score	The pruritus grading score includes four areas each has its score: distribution score 1-3;1= single site and 3 generalized, Severity score 1-5 ; 1= rubbing,5 = general excoriation, Frequency score 1-5; 1= episodic,5= continuous, and Sleep disturbance score 0-6 ; 0= no effect on sleep, 6= total restless.	four months
Secondary	Changes in the liver function test and lipid profile	investigate the effect on Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST) ,Albumin,Bilirubin, Bile acid, lipid profile	four months

External Links

•   Review article