Fibrates in Pediatric Cholestasis

Fibrates: An Adjuvant Therapy for Cholestasis In Pediatric Age Group

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

Study Overview

• Status: Completed
• Conditions: Chronic Cholestasis
• Intervention / Treatment: Drug: Ursogal; Drug: Lipanthyl

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Shibīn Al Kawm, Egypt
    • National liver istitute
  • Nasr City
    • Cairo, Nasr City, Egypt
      • Dr. Yassin Abdel Ghaffar Charity Center For Liver Diseases & Researches

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ursogal; Control group : Ursogal 10-20 mg/kg/d on 2 divided dose for four months with regular follow up.	Drug: Ursogal; suspension; Other Names: non
Experimental: Lipanthyl + Ursogal; Therapy group: Ursogal 10-20 mg/kg/d by mouth, on 2 divided dose, and lipanthyl 10-20 mg/kg/d by mouth,once per day, for four months with regular follow up.	Drug: Ursogal; suspension; Other Names: non; Drug: Lipanthyl; Tablet; Other Names: ursogal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Hoda A. Atta
• Investigators: Study Director: Tawhida Y Abdel Ghaffar, MD, ASU

Publications and helpful links

General Publications

• 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.

Helpful Links

• Review article

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 20, 2018

Study Registration Dates

• First Submitted: July 2, 2018
• First Submitted That Met QC Criteria: July 2, 2018
• First Posted (Actual): July 13, 2018

Study Record Updates

• Last Update Posted (Actual): July 17, 2018
• Last Update Submitted That Met QC Criteria: July 14, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: pediatric cholestasis, Fibrate
• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gastrointestinal Agents; Hypolipidemic Agents; Lipid Regulating Agents; Cholagogues and Choleretics; Fenofibrate; Ursodeoxycholic Acid
• Other Study ID Numbers: 1984

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Only overall results will be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No