AzTrials
AzTrials

Hereditary DiseasesPhase 2/3NCT04531878

BSEP Function Rescue During Childhood Inhereditary Cholestatic Diseases

A Phase 2/3 study testing 4-Phenylbutyrate in people with Hereditary Diseases and Cholestasis, Intrahepatic, run by Children's Hospital of Fudan University.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

The purpose of the study is to improve the prognosis of inhereditary cholestasis caused by ABCB11 gene mutations by using BSEP function rescue drugs Read more about this study

Who is it for?
Ages 2 months to 18 years
What is being tested?
4-Phenylbutyrate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
8 Feb 2023to 8 Feb 2023
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 months to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • with signed informed consent form from the guardian, and the patient if applicable.
  • aged from 2 month to 18 years old.
  • with cholestatic disease caused by ABCB11 biallelic mutation.
  • Long-term residence in China.

Who cannot join

  • Currently receiving or previously received experimental drugs.
  • The child is already in the stage of liver failure, or in unstable state that are not suitable for drug treatment according to the researcher's judgment: serious complications such as bleeding tendency and skin rash.
  • accompany with other chronic liver disease (viral hepatitis B and C, autoimmune hepatitis, wilson disease, cystic fibrosis, primary biliary cirrhosis, biliary atresia, sclerosing cholangitis, bile acid synthesis defects, and infections, cholestasis caused by space-occupying and other reasons).
  • Suffered from congenital TORCHES infection, including toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus, EB virus, syphilis, HIV, etc.
  • With any other major medical conditions that may affect drug absorption, metabolism, or excretion based on the researcher's judgment.
  • Known or suspected hypersensitivity to any experimental drugs or their indigents.
  • Patients with alcohol or drug dependence.
  • In receiving any investigational drugs or within 60 days before enrollment.

About this study

Official title: Jian-She Wang of Children's Hospital of Fudan University

The purpose of the study is to improve the prognosis of inhereditary cholestasis caused by ABCB11 gene mutations by using BSEP function rescue drugs

Read the detailed description

Bile acids function as detergents to aid digestion and as signaling molecules to regulate gene expression and metabolism. They are synthesized from cholesterol in the liver, secreted into bile and re -turned from chyme to liver in portal- vein blood 6-10 times per day (enterohepatic circulation. Enterohepatic circulation of bile acids involves more than 20 transporters among which bile salt export pump (BSEP), encoded by ABCB11 plays a key role. BSEP medi-ates the secretion of bile acids across the canalicular membrane of hepatocytes into bile to provide the osmotic pressure for bile flow. Mutations in ABCB11 can cause absence or dysfunction of BSEP leading to cholestasis. Bile acid accumulation in hepatocytes caused by BSEP dysfunction is associated with a range of liver dis-eases, ranging from transient neonatal cholestasis to fatal progressive familial intrahepatic cholestasis (PFIC), with jaundice, growth retardation, cirrhosis, liver failure and death. Our current indicates that more than 70% patents with ABCB11 mutations need liver-transplantation or dead during follow-up. In recent years, some targeted drugs including 4-phenylbutyrate(for patients with BSEP trafficking abnormal), ivacaftor(for patients with abnormal BSEP transport function), and gentamicin (for patients with none sense mutations) have emerged make it possible for individual targeted therapy possible.

Being tested
4-Phenylbutyrate
Keywords
BSEP, ABCB11, biliary diversion, liver biopsy, gene
Medical subject headings
Genetic Diseases, Inborn, Cholestasis, Intrahepatic, Cholestasis, progressive familial intrahepatic 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 4-PhenylbutyrateDrug

    Also called UDCA or biliary diversion

    4-phenylbutyrate therapy will be started at a daily dose of 200 mg kg/d divided in 2 oral doses of sodium phenylbutyrate (AMMONAPS, Swedish Orphan Inter AB). In order to get the best effect, the dose will be increased up to a maximum of 500 mg kg/d.

Study groups in NCT04531878
Study groupRoleWhat they receive
BSEP trafficking abnormal groupExperimentalPatients with ABCB11 missense mutations that were speculated to affect the BSEP trafficking
Receives: Drug: 4-Phenylbutyrate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Native liver survive time

    Time of patient survived with native liver will be accessed.

    Measured: During follow-up (about 3 years）

Secondary outcomes (14)

  1. ALT(Alanine Aminotransferase)

    It is a repeated measurement variable. ALT would be measured.

    Measured: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

  2. DB(direct bilirubin) levels

    It is a repeated measurement variable. DB would be measured.

    Measured: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

  3. TB(total bilirubin)

    It is a repeated measurement variable. TB would be measured.

    Measured: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

  4. AST(Aspartate Aminotransferase)

    It is a repeated measurement variable. AST would be measured.

    Measured: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

  5. Weight

    It is a repeated measurement variable. The weight of the patients.

    Measured: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

  6. Length

    It is a repeated measurement variable. The length of the patients

    Measured: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

  7. Itching relief

    It is a repeated measurement variable.The itching score level will be accessed using a score ranged from 0 to 10.

    Measured: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

  8. Liver pathological staging

    It is a repeated measurement variable.Liver pathological staging will be accessed using the Batts-Ludwig system.

    Measured: day 90, 180

  9. Coagulation function

    It is a repeated measurement variable.The INR(international normalized ratio)/PT(prothrombin time) levels will be followed if with coagulation function abnormal.

    Measured: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

  10. Hypoglycemia

    It is a repeated measurement variable.The glucose wil be followed.

    Measured: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

  11. Hypo25-hydroxyvitamin Demia

    It is a repeated measurement variable. Hypo25-hydroxyvitamin D levels will be followed.

    Measured: at day 0, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

  12. The bile acid profiling

    It is a repeated measurement variable. The bile acid profiling will be checked during follow-up.

    Measured: at day 30, 60, 90, 180, 360, 720 and 1080

  13. Hypoproteinemia

    It is a repeated measurement variable. The albumin wil be followed.

    Measured: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080

  14. Adverse events

    It is a binary variable(1/0). If any adverse events including bleeding, fractures, tumors, and hepatic encephalopathy happended during the follow-up, the variable would be setted into "1". The incidence of each adverse events will also be calculated.

    Measured: During follow-up (about 3 years）

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2020
  2. Study start8 Feb 2023 (estimated)
  3. Primary completion8 Feb 2023
  4. Study completion8 Feb 2023

Why it stopped: lack of funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04531878
Sponsor's protocol ID
BSEP_FudanEK_001
Status last verified
Feb 2023
First submitted
26 Aug 2020
Last updated
9 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing 4-Phenylbutyrate in people with Hereditary Diseases and Cholestasis, Intrahepatic, run by Children's Hospital of Fudan University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 9 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Native liver survive time (time frame: During follow-up (about 3 years）). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04531878.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in