GCSF Adjunct Therapy for Biliary Atresia (BA_GCSF)

February 12, 2020 updated by: Holterman, Ai-Xuan, M.D.

Granulocyte-Colony Stimulating Factor Adjunct Therapy for Biliary Atresia

The Investigators propose to test the hypothesis that GCSF therapy enhances the clinical outcome of Kasai operated Biliary Atresia (BA) patients. In this study, Investigators will conduct a dose determination for GCSF use in post Kasai subjects to support a future phase 2 efficacy study. The first 3 post Kasai BA subjects with liver biopsy-confirmed BA will be given 5 ug/kg/d of GCSF in 3 daily subcutaneous doses starting on post Kasai day 3. A second group of 3 subjects will be assigned to the 10 ug/Kg/d dose after the 5ug/kg/d dose has been proven to be safe. The levels of circulating hematopoietic stem cells and a 1-month safety profile will be analyzed.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In BA, neonatal fibrous obliteration of the biliary tract obstructs biliary drainage and promotes biliary fibrosis. BA is the leading cause of pediatric chronic end-stage liver disease and pediatric liver transplantation. Relief of cholestasis by the Kasai portoenterostomy is only partly successful with continued progression of fibrosis to hepatic insufficiency and, for long term survival, with eventual need for liver transplantation in the majority of the patients. In animal models of liver injury, GCSF enhances hematopoietic stem cell HSC mobilization and engraftment in the liver with associated improved liver repair response and attenuated hepatic necrosis and fibrosis. Randomized controlled trials of GCSF intervention for chronic liver failure in adult patients with acute hepatic decompensation showed improved short-term survival and hepatic indices such the model for end-stage liver disease (MELD) scores.

The Investigators propose that post Kasai GCSF therapy attenuates biliary fibrosis and progression to cirrhosis. The objectives are meant to demonstrate that Kasai-GCSF sequential therapy improves biliary drainage, and delays the progression of hepatic insufficiency. Toward this goal, Investigators will first evaluate in post Kasai subjects the maximum tolerated dose of GCSF in mobilizing circulating CD34+ hematopoietic stem cells, with the limiting dose based on GCSF-related severe adverse effects. A one-month safety of GCSF will be tested with the 2 standard doses of 5 ug/kg/d and 10 ug/kg/d.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
  • Vietnam
      • Hanoi, Vietnam
        • National Childrens Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 weeks to 5 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Completed the preliminary work up for cholestasis with suspected or inconclusive diagnosis of BA
  2. Gestational Age > 36wks
  3. Weight > 2 Kg
  4. Age >-2 weeks-<180 days at diagnosis
  5. Serum Direct Bilirubin > 2 mg/dL GGT > 100 U/L
  6. Kasai operated patients for Type 3 or 4 anatomy of BA
  7. Cholangiogram/porta hepatis findings diagnostic of BA
  8. Liver biopsy supporting BA diagnosis

Exclusion Criteria:

  1. Having access to liver transplantation for immediate Kasai failure
  2. Prior Kasai patients
  3. Major cardiac, renal, CNS malformations with poor prognosis
  4. Intracranial hemorrhage
  5. History of recent TPN use within the last 2 weeks of surgery
  6. GI tract obstruction
  7. Laparoscopic Kasai repair

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose determination GCSF
Time Frame: 13 months
To determine the maximum tolerated dose of GCSF based on GCSF dose limiting toxicity and the extent of peripheral blood stem cell mobilization as measured by increases in CD34+cells with upper levels limited by white blood cells (WBCs) less than 50,000 per microliter (mcL) of blood.
13 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Holterman, Ai-Xuan, M.D.

Collaborators

Children's National Health System
T. Rose Clinical, Inc., United States
Big Leap Research, Vietnam

Investigators

  • Principal Investigator: Evan P Nadler, MD, Children's National Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 15, 2018

Primary Completion (Actual)

January 31, 2020

Study Completion (Actual)

January 31, 2020

Study Registration Dates

First Submitted

December 22, 2017

First Submitted That Met QC Criteria

January 3, 2018

First Posted (Actual)

January 9, 2018

Study Record Updates

Last Update Posted (Actual)

February 17, 2020

Last Update Submitted That Met QC Criteria

February 12, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR00005169
  • IND 119679-0007 (Other Identifier: Food and Drug Administration)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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