Infantile Refsum's DiseasePhase 3NCT00007020
Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid
A Phase 3 study testing Cholic Acids in people with Infantile Refsum's Disease and Zellweger Syndrome, run by Mirum Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
OBJECTIVES: I. To Evaluate the therapeutic efficacy of cholic acid during provision of compassionate treatment to patients with identified inborn errors of bile acid synthesis and metabolism II. To assess the safety and tolerability of cholic acid Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Infantile Refsum's Disease, Zellweger Syndrome, Adrenoleukodystrophy
- What is being tested?
- Cholic Acids
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 1992to Dec 2009
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Infants < age 3 months
- Children presenting for evaluation of cholestasis defined as a conjugated bilirubin > 2mg/dl or increased serum bile acids
- Older subjects of any age with cholestatic liver disease if urine screens suggested that they had inborn errors of bile acid metabolism
- Confirmation of a diagnosis of an inborn error of bile acid synthesis based upon urine analysis by FAB-MS to determine whether specific abnormalities in bile acid synthesis are indicated
- The patient and/or parent/legal guardian must have signed the written informed consent document before study start.
- The patient must be willing and able to comply with all study assessments and procedures.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
About this study
Official title: Investigation in the Pathogenesis of Liver Disease in Patients With Inborn Errors of Bile Acid Metabolism
OBJECTIVES:
- To Evaluate the therapeutic efficacy of cholic acid during provision of compassionate treatment to patients with identified inborn errors of bile acid synthesis and metabolism
II. To assess the safety and tolerability of cholic acid
Read the detailed description
Investigational Plan:
A Phase III, open label, single arm, nonrandomized, non-comparative, compassionate treatment study of cholic acid in the treatment of defects of bile acid metabolism.
The study was begun with a single study site at Cincinnati Children's Hospital Medical Center (CCHMC), but in 2005 was expanded so that compassionate treatment could be provided to additional patients who had been identified with inborn errors of bile metabolism through the center's screening/diagnostic program.
Patients who were screened were contacted and evaluated with respect to the inclusion/exclusion criteria. Signed informed consent by the patient and/or parents/legal guardian was obtained as soon as it is confirmed that the patient met inclusion/exclusion criteria and the parents/guardian would agree for the child to participate in the study.
The primary interventions for the study were:
- Administration of study drug.
- Collection of baseline physical exam, vital signs, blood and urine samples for laboratory tests.
- Collection of periodic physical exam, vital signs, blood and urine samples for laboratory tests during the period of administration of the study drug.
- Collection of any adverse event information.
Time and Events Schedule:
Baseline:
- Confirm eligibility
- Obtain written informed consent from patient and/or parents/legal guardian
- Collect demographic data and disease and medication history, including family history Baseline and Ongoing:
- Obtain body weight
- Record adverse events
- Obtain blood and urine samples for laboratory tests
- Initiate study drug therapy \& monitor study drug therapy and adjust dose as needed
- Conditions
- Infantile Refsum's Disease, Zellweger Syndrome, Adrenoleukodystrophy, Peroxisomal Disorders, Cholestasis
- Being tested
- Cholic Acids
- Medical subject headings
- Refsum Disease, Infantile, Zellweger Syndrome, Adrenoleukodystrophy, Peroxisomal Disorders, Cholestasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cholic AcidsDrug
Also called Cholic, Cholic Acid, Cholic Acid Capsules
10-15 mg/kg body weight/day taken orally.
| Study group | Role | What they receive |
|---|---|---|
| Cholic Acid | Other | Not described Receives: Drug: Cholic Acids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Excretion of Atypical Bile Acids in Urine by Category
Patients with excretion of atypical bile acids in urine by category, from worst status before treatment (baseline, BL) to best status on treatment (OT)
Measured: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Secondary outcomes (4)
Change in Liver Function Tests (LFTs) Measured in Serum
Patients with elevations of liver function tests (alanine transaminase [ALT], aspartate transaminase [AST]) measured as multiples of the upper limit of normal (ULN) at baseline (worst value) and on treatment (best value)
Measured: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Liver Histology
Patients (number, percentage) with pathological findings for qualitative (the presence of inflammation, fibrosis, necrosis, giant cells and cholestasis) and quantitative (the degrees of the aforementioned histologic features) liver histopathology at baseline (BL) and on treatment (OT).
Measured: At baseline (if no historical data were available) and between 1 and 6 months following treatment start.
Height and Weight
Change in height/weight percentiles from baseline (worst value) to the best on-treatment value, based on CDC (Centres for Disease Control and Prevention, US) growth chart percentiles
Measured: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Adverse Events
Number of patients with any adverse event
Measured: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2000 (estimated)
- Study startJan 1992
- Primary completionDec 2009
- Study completionDec 2009
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 (1)Papers the sponsor has linked to this study.
- Other trials for Infantile Refsum's DiseaseStudies of the same condition, open and under way.
- More trials run by Mirum Pharmaceuticals, Inc.The 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
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mirum Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Children's Hospital Medical Center, Cincinnati
- Responsible party
- Sponsor
- Investigators
- James Heubi, MD, Principal investigator, Children's Hospital Medical Center, CincinnatiKenneth Setchell, PhD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00007020
- Sponsor's protocol ID
- CAC-91-10-10
- Other IDs
- CCHMC-91-10-10, NCRR-M01RR08084-0009
- Status last verified
- Sep 2023
- First submitted
- 6 Dec 2000
- Last updated
- 3 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Heubi JE, Bove KE, Setchell KDR. Oral Cholic Acid Is Efficacious and Well Tolerated in Patients With Bile Acid Synthesis and Zellweger Spectrum Disorders. J Pediatr Gastroenterol Nutr. 2017 Sep;65(3):321-326. doi: 10.1097/MPG.0000000000001657.
PubMed 28644367
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation in the Pathogenesis of Liver Disease in Patients With Inborn Errors of Bile Acid Metabolism
- ClinicalTrials.gov ID
- NCT00007020
- Acronym / sponsor ID
- CAC-91-10-10
- Conditions
- Infantile Refsum's Disease, Zellweger Syndrome, Adrenoleukodystrophy, Peroxisomal Disorders, Cholestasis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Mirum Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Children's Hospital Medical Center, Cincinnati
- Study start
- Jan 1992
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 7 Dec 2000 (estimated)
- Results
- Posted 15 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
OBJECTIVES:
- To Evaluate the therapeutic efficacy of cholic acid during provision of compassionate treatment to patients with identified inborn errors of bile acid synthesis and metabolism
II. To assess the safety and tolerability of cholic acid
Detailed description
Investigational Plan:
A Phase III, open label, single arm, nonrandomized, non-comparative, compassionate treatment study of cholic acid in the treatment of defects of bile acid metabolism.
The study was begun with a single study site at Cincinnati Children's Hospital Medical Center (CCHMC), but in 2005 was expanded so that compassionate treatment could be provided to additional patients who had been identified with inborn errors of bile metabolism through the center's screening/diagnostic program.
Patients who were screened were contacted and evaluated with respect to the inclusion/exclusion criteria. Signed informed consent by the patient and/or parents/legal guardian was obtained as soon as it is confirmed that the patient met inclusion/exclusion criteria and the parents/guardian would agree for the child to participate in the study.
The primary interventions for the study were:
- Administration of study drug.
- Collection of baseline physical exam, vital signs, blood and urine samples for laboratory tests.
- Collection of periodic physical exam, vital signs, blood and urine samples for laboratory tests during the period of administration of the study drug.
- Collection of any adverse event information.
Time and Events Schedule:
Baseline:
- Confirm eligibility
- Obtain written informed consent from patient and/or parents/legal guardian
- Collect demographic data and disease and medication history, including family history Baseline and Ongoing:
- Obtain body weight
- Record adverse events
- Obtain blood and urine samples for laboratory tests
- Initiate study drug therapy \& monitor study drug therapy and adjust dose as needed
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cholic Acid | Other | Drug: Cholic Acids |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Infants < age 3 months
- Children presenting for evaluation of cholestasis defined as a conjugated bilirubin > 2mg/dl or increased serum bile acids
- Older subjects of any age with cholestatic liver disease if urine screens suggested that they had inborn errors of bile acid metabolism
- Confirmation of a diagnosis of an inborn error of bile acid synthesis based upon urine analysis by FAB-MS to determine whether specific abnormalities in bile acid synthesis are indicated
- The patient and/or parent/legal guardian must have signed the written informed consent document before study start.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Cholic AcidsAlso: Cholic, Cholic Acid, Cholic Acid Capsules10-15 mg/kg body weight/day taken orally. | Drug | Cholic Acid |
Primary outcome
Number of Participants With Excretion of Atypical Bile Acids in Urine by Category
Time frame: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Patients with excretion of atypical bile acids in urine by category, from worst status before treatment (baseline, BL) to best status on treatment (OT)
4 secondary outcomes
Change in Liver Function Tests (LFTs) Measured in Serum
Time frame: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Liver Histology
Time frame: At baseline (if no historical data were available) and between 1 and 6 months following treatment start.
Height and Weight
Time frame: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Adverse Events
Time frame: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28644367Heubi JE, Bove KE, Setchell KDR. Oral Cholic Acid Is Efficacious and Well Tolerated in Patients With Bile Acid Synthesis and Zellweger Spectrum Disorders. J Pediatr Gastroenterol Nutr. 2017 Sep;65(3):321-326. doi: 10.1097/MPG.0000000000001657.
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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.
James Heubi, MD principal investigator
Children's Hospital Medical Center, Cincinnati
Kenneth Setchell, PhD 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 Cholic Acids in people with Infantile Refsum's Disease and Zellweger Syndrome, run by Mirum Pharmaceuticals, Inc. 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 6 inclusion and 0 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 3 Oct 2023. 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 15 Jul 2020). 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?
Number of Participants With Excretion of Atypical Bile Acids in Urine by Category (time frame: Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 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 NCT00007020, which also lists 1 linked publication.
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 3 Oct 2023.