Gastrostomy-Biliary Diversion: Innovative Management for Bile Canalicular Transport Disorders

Gastrostomy-Biliary Diversion: Innovative Management for Children With Bile Canalicular Transport Disorders

Progressive familial intrahepatic cholestasis (PFIC) is a group of disorders that can present early in life with cholestasis and intractable pruritus. Their treatment poses a great challenge, with medical treatment is not successful in many cases. Moreover, the available non-transplant surgeries carry many side effects and different degrees of efficacy. Partial external biliary diversion, internal biliary diversion, and ileal exclusion still lack widespread experience with many side effects. Nasobiliary stent placement has little tolerability, especially in younger age. Gastrobiliary tube is a novel modality for external biliary diversion in such patients.

Study Overview

• Status: Unknown
• Conditions: Progressive Familial Intrahepatic Cholestasis
• Intervention / Treatment: Device: Gastostomy-biliary tube; Device: External biliary diversion, internal biliary diversion and nasobiliary tube

Detailed Description

Progressive familial intrahepatic cholestasis (PFIC) is a group of disorders that can present early in life with cholestasis and intractable pruritus. They result primarily from defective transporters of different bile constituents on the canalicular membrane. The mildest form of these defective transporters can present by what is called benign recurrent intrahepatic cholestasis (BRIC).

More recently both disease categories that represent the severest (PFIC) and mildest (BRIC) forms of these transporters are better nomenclated as bile canalicular transport disorders, as some cases can start early as BRIC and later in life progress the PFIC phenotype. Moreover, a continuous spectrum of severity is present between what were previously known as PFIC and BRIC.

If the severest forms are not treated effectively they can have devastating outcomes reaching death. On the other hand, those known as BRIC can have severe attacks with unremitting pruritus that could be prolonged and sometimes persistent.

Their treatment poses a great challenge, with medical treatment is not successful in many cases. Moreover, the available non-transplant surgeries carry many side effects and different degrees of efficacy. Partial external biliary diversion is not always successful and has disfiguring effects and the stoma can have many side effects. Internal biliary diversion and ileal exclusion still lack widespread experience and encouraging results due to sometimes lack of efficacy and others due to side effects. Nasobiliary stent placement was tried in previous cases with a promising outcome, but with little tolerability, especially in younger age.

In spite liver transplant is the last resort for failing cases, the availability of successful non transplant therapy would be the preferable one if it is with adequate efficacy and little side effects. The innovative intervention proposed in this study is expected to have a good efficacy due to total biliary diversion rather than the partial ones obtained by other surgeries. Moreover, it avoids the disfiguring impact of the jeujenal stoma. More importantly, it can be removed at any time and be used at the times of severe flare of the disease.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ahmad M Sira, M.D.; Phone Number: +2-048-222-2740; Email: asira@liver.menofia.edu.eg; ahmadsira@hotmail.com

Study Locations

• Egypt
  • Menofiya
    • Shibīn Al Kawm, Menofiya, Egypt, 32511
      • Recruiting
      • Pediatric Hepatology, Gastroenterology and Nutrition Department, National Liver Institute, Menoufia University
      • Contact: Ahmad M Sira, M.D.; Phone Number: +2-048-222-2740; Email: asira@liver.menofia.edu.eg; ahmadsira@hotmail.com
      • Sub-Investigator: Hanaa A El-Araby, MD
      • Sub-Investigator: Hosam-Eldin M Basiouny, MD
      • Sub-Investigator: Hadeer S Allam, M.B.;B.Ch.
      • Sub-Investigator: Esam A Elsheimy, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• PFIC cases that are previously responding to medical treatment with recent flare of the disease that doesn't respond to medical therapy
• PFIC cases that are not responding to medical treatment and refusing non-transplant surgery and not indicated for liver transplant
• BRIC cases with frequent attacks not responding to medical therapy and refusing or unable to tolerate nasobiliary stent

Exclusion Criteria:

• Severe portal hypertensive gastropathy
• Decompensated cirrhosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Gastrostomy-biliary tube; The study group will be subjected to gastrostomy followed by ERCP with nasobiliary stent placement in the CBD with its distal end been exit from the previously performed gastrostomy instead of the nostril	Device: Gastostomy-biliary tube; gastrostomy followed by ERCP with nasobiliary stent placement in the CBD with its distal end been exit from the previously performed gastrostomy instead of the nostril
EXPERIMENTAL: Other biliary diversion modalities; The control group will include those cases with other modalities of therapy as external biliary diversion, internal biliary diversion, and nasobiliary tube	Device: External biliary diversion, internal biliary diversion and nasobiliary tube; All biliary diversion modalities other than gastrobiliary tube

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of bleeding	number of patients with bleeding	6 months
Occurrence of infection	number of patients with infection	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum bilirubin level	number of patients with normal bilirubin	12 months
Improvement of pruritus	number of patients with no pruritus	12 months

Collaborators and Investigators

• Sponsor: National Liver Institute, Egypt
• Investigators: Principal Investigator: Ahmad M Sira, M.D., Pediatric Hepatology Dep; National Liver Institute, Menoufia University, Egypt

Publications and helpful links

General Publications

• van der Woerd WL, van Mil SW, Stapelbroek JM, Klomp LW, van de Graaf SF, Houwen RH. Familial cholestasis: progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy. Best Pract Res Clin Gastroenterol. 2010 Oct;24(5):541-53. doi: 10.1016/j.bpg.2010.07.010.
• Kaur S, Sharma D, Wadhwa N, Gupta S, Chowdhary SK, Sibal A. Therapeutic interventions in progressive familial intrahepatic cholestasis: experience from a tertiary care centre in north India. Indian J Pediatr. 2012 Feb;79(2):270-3. doi: 10.1007/s12098-011-0516-8. Epub 2011 Jul 19.
• Mochizuki K, Obatake M, Takatsuki M, Nakatomi A, Hayashi T, Okudaira S, Eguchi S. Partial internal biliary diversion for patients with progressive familial intrahepatic cholestasis type 1. Pediatr Surg Int. 2012 Jan;28(1):51-4. doi: 10.1007/s00383-011-3018-x.
• Stapelbroek JM, van Erpecum KJ, Klomp LW, Venneman NG, Schwartz TP, van Berge Henegouwen GP, Devlin J, van Nieuwkerk CM, Knisely AS, Houwen RH. Nasobiliary drainage induces long-lasting remission in benign recurrent intrahepatic cholestasis. Hepatology. 2006 Jan;43(1):51-3. doi: 10.1002/hep.20998.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 10, 2020
• Primary Completion (ANTICIPATED): October 1, 2020
• Study Completion (ANTICIPATED): April 1, 2021

Study Registration Dates

• First Submitted: August 25, 2019
• First Submitted That Met QC Criteria: August 25, 2019
• First Posted (ACTUAL): August 28, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 24, 2020
• Last Update Submitted That Met QC Criteria: August 20, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: bile canalicular transport disorders
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis; Cholestasis, Intrahepatic
• Other Study ID Numbers: GBD-PED-BCTD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No