Bile Acid Synthesis DefectPhase 3NCT01589523
GlycoCholic Acid Treatment for Patients With Inborn Errors in Bile Acid Synthesis
A Phase 3 study testing Glycocholic Acid in people with Bile Acid Synthesis Defect and Inborn Error of Bile Acid Metabolism, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial summary
The purpose of this research study is to determine the way (mechanisms) by which your defect in bile acid handling (metabolism) causes your liver disease or abnormality in absorption of vitamins and the effect of an investigational bile acid therapy (glycocholic acid) on your vitamin absorption and your liver disease. Read more about this study
- Who is it for?
- Ages 1 week to 85 years
- Conditions the study is for
- Bile Acid Synthesis Defect, Inborn Error of Bile Acid Metabolism, Inborn Error of Bile Acid Conjugation
- What is being tested?
- Glycocholic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2006to 22 Jan 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 week to 85 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Confirmation of a diagnosis of an inborn error of bile acid synthesis/conjugation based upon urine analysis by FAB-MS.
- Any age
- Participant must be willing and able to comply with study assessments and procedures.
- The participant and/or parent/legal guardian must have signed the written informed consent document prior to study start.
Who cannot join
- 1. No confirmed diagnosis of inborn error of bile acid synthesis/conjugation based upon urine analysis by FAB-MS.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: Conjugated Cholic Acid for the Treatment of Inborn Errors in Bile Acid Synthesis Involving Side-Chain Conjugation
The purpose of this research study is to determine the way (mechanisms) by which your defect in bile acid handling (metabolism) causes your liver disease or abnormality in absorption of vitamins and the effect of an investigational bile acid therapy (glycocholic acid) on your vitamin absorption and your liver disease. An investigational therapy is one that not approved by the United States Food and Drug Administration (FDA) and is being provided to you under an Investigational New Drug application from the FDA.
Read the detailed description
Inborn errors of bile acid metabolism have been established as a well recognized cause of neonatal cholestasis and fat-soluble vitamin malabsorption. Although there is extensive experience with metabolic defects in the biosynthetic pathway, few patients have identified with defects in conjugation with taurine or glycine that allows bile acids to become effective detergents. This protocol is designed to study the effect of defects of conjugation of bile acids on growth and fat-soluble vitamin malabsorption. Study subjects will have liver function studies performed, serum and urinary bile acid measurements, vitamin levels, growth measurements, bile acid pool size measurements made by stable isotope dilution mass-spectrometry, and measurements of absorption of two fat-soluble vitamins, tocopherol and vitamin D. Subjects will be treated orally with conjugates of cholic acid with follow-up laboratories performed as an outpatient and then subjects will have all of the initial studies repeated during an inpatient stay 3-12 months after starting treatment. Subjects with previous liver biopsies indicating the presence of significant liver disease will have a repeat liver biopsy after 3-12 months treatment to assess the histologic response to treatment.
- Conditions
- Bile Acid Synthesis Defect, Inborn Error of Bile Acid Metabolism, Inborn Error of Bile Acid Conjugation
- Being tested
- Glycocholic Acid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glycocholic AcidDrug
Also called Conjugated Cholic Acid
10-15mg/kg body weight/day taken orally. Supplied as either liquid or 50mg capsules.
| Study group | Role | What they receive |
|---|---|---|
| GlycoCholic Acid, Study Drug | Experimental | An open label, single arm, non-randomized, non-comparative, treatment study of Glycocholic Acid in the treatment of defects of bile acid metabolism. Receives: Drug: Glycocholic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Conjugated Cholic Acid (GCA) for the Treatment of Inborn Errors in Bile Acid Synthesis Involving Side-chain Conjugation.
This is the number of participants with bile acid amidation defects treated with oral glycocholic acid (15 milligrams/kilograms (mg/kg) of body weight/day (bw/day))
Measured: Up to 10 years
Evaluation of Levels of Atypical Bile Acid Metabolites After GCA Treatment Compared
Semi-quantitative descriptive evaluation of the levels of atypical bile acids in urine measured by mass spectrometry (FAB MS) based on a scale of 0 = absent or traces levels, 1 = low levels, 2 = moderate levels, 3 = high levels using the signal/noise ratio and intensity of ions. Atypical bile acids evaluated included m/z 407 (unconjugated cholic acid), m/z 471 (dihydroxy-choleanoic-sulfate) and m/z 583 (trihydroxy-choleanoic glucuronide).
Measured: Average of 6 months, average 12 months, and average of after year 1 to 10 years
Secondary outcomes (3)
Changes in Liver Function Tests of ALT From Baseline to Post-treatment
Liver function tests Alanine Aminotransferease (ALT)
Measured: Comparison between baseline and post-treatment (average of available timepoints after year 1 through year 10)
Change in Liver Function Test: AST From Baseline to Post-treatment
Measure of Aspartate Aminotransferase (AST)
Measured: Comparison between baseline and post-treatment (average of available timepoints after year 1 through year 10)
Change in Vitamin D, 25-OH Measure From Baseline to Post-treatment
Measure Vitamin D levels nanograms per milliliter (ng/mL)
Measured: Pre-treatment and post treatment (average of available timepoints after year 1 through year 10)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2012 (estimated)
- Study startFeb 2006
- Primary completion22 Jan 2019
- Study completion22 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Bile Acid Synthesis DefectStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kenneth D. Setchell, Ph.D., Principal investigator, Children's Hospital Medical Center, CincinnatiJames E. Heubi, M.D., Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01589523
- Sponsor's protocol ID
- 2009-0780
- Status last verified
- May 2022
- First submitted
- 3 Apr 2012
- Last updated
- 8 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Setchell KD, Heubi JE, Shah S, Lavine JE, Suskind D, Al-Edreesi M, Potter C, Russell DW, O'Connell NC, Wolfe B, Jha P, Zhang W, Bove KE, Knisely AS, Hofmann AF, Rosenthal P, Bull LN. Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency. Gastroenterology. 2013 May;144(5):945-955.e6; quiz e14-5. doi: 10.1053/j.gastro.2013.02.004. Epub 2013 Feb 13.
PubMed 23415802Heubi JE, Setchell KD, Jha P, Buckley D, Zhang W, Rosenthal P, Potter C, Horslen S, Suskind D. Treatment of bile acid amidation defects with glycocholic acid. Hepatology. 2015 Jan;61(1):268-74. doi: 10.1002/hep.27401. Epub 2014 Dec 23.
PubMed 25163551
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Conjugated Cholic Acid for the Treatment of Inborn Errors in Bile Acid Synthesis Involving Side-Chain Conjugation
- ClinicalTrials.gov ID
- NCT01589523
- Acronym / sponsor ID
- 2009-0780
- Conditions
- Bile Acid Synthesis Defect, Inborn Error of Bile Acid Metabolism, Inborn Error of Bile Acid Conjugation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- Feb 2006
- Primary completion
- 22 Jan 2019 (actual)
- Study completion
- 22 Jan 2019 (actual)
- First posted
- 2 May 2012 (estimated)
- Results
- Posted 12 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to determine the way (mechanisms) by which your defect in bile acid handling (metabolism) causes your liver disease or abnormality in absorption of vitamins and the effect of an investigational bile acid therapy (glycocholic acid) on your vitamin absorption and your liver disease. An investigational therapy is one that not approved by the United States Food and Drug Administration (FDA) and is being provided to you under an Investigational New Drug application from the FDA.
Detailed description
Inborn errors of bile acid metabolism have been established as a well recognized cause of neonatal cholestasis and fat-soluble vitamin malabsorption. Although there is extensive experience with metabolic defects in the biosynthetic pathway, few patients have identified with defects in conjugation with taurine or glycine that allows bile acids to become effective detergents. This protocol is designed to study the effect of defects of conjugation of bile acids on growth and fat-soluble vitamin malabsorption. Study subjects will have liver function studies performed, serum and urinary bile acid measurements, vitamin levels, growth measurements, bile acid pool size measurements made by stable isotope dilution mass-spectrometry, and measurements of absorption of two fat-soluble vitamins, tocopherol and vitamin D. Subjects will be treated orally with conjugates of cholic acid with follow-up laboratories performed as an outpatient and then subjects will have all of the initial studies repeated during an inpatient stay 3-12 months after starting treatment. Subjects with previous liver biopsies indicating the presence of significant liver disease will have a repeat liver biopsy after 3-12 months treatment to assess the histologic response to treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GlycoCholic Acid, Study Drug | Experimental | Drug: Glycocholic AcidAn open label, single arm, non-randomized, non-comparative, treatment study of Glycocholic Acid in the treatment of defects of bile acid metabolism. |
Who may qualify
- Ages
- 1 week to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Confirmation of a diagnosis of an inborn error of bile acid synthesis/conjugation based upon urine analysis by FAB-MS.
- Any age
- Participant must be willing and able to comply with study assessments and procedures.
- The participant and/or parent/legal guardian must have signed the written informed consent document prior to study start.
Key exclusion criteria (1 listed)
- 1. No confirmed diagnosis of inborn error of bile acid synthesis/conjugation based upon urine analysis by FAB-MS.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Glycocholic AcidAlso: Conjugated Cholic Acid10-15mg/kg body weight/day taken orally. Supplied as either liquid or 50mg capsules. | Drug | GlycoCholic Acid, Study Drug |
Primary outcome
Conjugated Cholic Acid (GCA) for the Treatment of Inborn Errors in Bile Acid Synthesis Involving Side-chain Conjugation.
Time frame: Up to 10 years
This is the number of participants with bile acid amidation defects treated with oral glycocholic acid (15 milligrams/kilograms (mg/kg) of body weight/day (bw/day))
Evaluation of Levels of Atypical Bile Acid Metabolites After GCA Treatment Compared
Time frame: Average of 6 months, average 12 months, and average of after year 1 to 10 years
Semi-quantitative descriptive evaluation of the levels of atypical bile acids in urine measured by mass spectrometry (FAB MS) based on a scale of 0 = absent or traces levels, 1 = low levels, 2 = moderate levels, 3 = high levels using the signal/noise ratio and intensity of ions. Atypical bile acids evaluated included m/z 407 (unconjugated cholic acid), m/z 471 (dihydroxy-choleanoic-sulfate) and m/z 583 (trihydroxy-choleanoic glucuronide).
3 secondary outcomes
Changes in Liver Function Tests of ALT From Baseline to Post-treatment
Time frame: Comparison between baseline and post-treatment (average of available timepoints after year 1 through year 10)
Change in Liver Function Test: AST From Baseline to Post-treatment
Time frame: Comparison between baseline and post-treatment (average of available timepoints after year 1 through year 10)
Change in Vitamin D, 25-OH Measure From Baseline to Post-treatment
Time frame: Pre-treatment and post treatment (average of available timepoints after year 1 through year 10)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23415802Setchell KD, Heubi JE, Shah S, Lavine JE, Suskind D, Al-Edreesi M, Potter C, Russell DW, O'Connell NC, Wolfe B, Jha P, Zhang W, Bove KE, Knisely AS, Hofmann AF, Rosenthal P, Bull LN. Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency. Gastroenterology. 2013 May;144(5):945-955.e6; quiz e14-5. doi: 10.1053/j.gastro.2013.02.004. Epub 2013 Feb 13.
- Results publication: PubMed 25163551Heubi JE, Setchell KD, Jha P, Buckley D, Zhang W, Rosenthal P, Potter C, Horslen S, Suskind D. Treatment of bile acid amidation defects with glycocholic acid. Hepatology. 2015 Jan;61(1):268-74. doi: 10.1002/hep.27401. Epub 2014 Dec 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth D. Setchell, Ph.D. principal investigator
Children's Hospital Medical Center, Cincinnati
James E. Heubi, M.D. principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Glycocholic Acid in people with Bile Acid Synthesis Defect and Inborn Error of Bile Acid Metabolism, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
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 1 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: finished, as of the sponsor's last update on 8 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 phase mean?
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?
Yes. Results are posted in the registry (first posted 12 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Conjugated Cholic Acid (GCA) for the Treatment of Inborn Errors in Bile Acid Synthesis Involving Side-chain Conjugation. (time frame: Up to 10 years). The study lists 2 primary outcomes in all. 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 NCT01589523, which also lists 2 linked publications.
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 8 Jun 2022.