Smith-Lemli-Opitz SyndromePhase 1/2NCT03720990
Smith-Lemli-Opitz Syndrome and Cholic Acid
A Phase 1/2 study testing Cholic Acid in people with Smith-Lemli-Opitz Syndrome, run by University of Nebraska at 2 sites in United States.
Trial summary
The purpose of this study is to determine whether dietary cholic acid therapy benefits people with Smith-Lemli-Opitz syndrome (SLOS) by leading to an increase in plasma cholesterol and reduction in harmful cholesterol precursors. Read more about this study
- Who is it for?
- Ages 2 to 25 years
- Conditions the study is for
- Smith-Lemli-Opitz Syndrome
- What is being tested?
- Cholic Acid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- 27 Mar 2021to 30 Sep 2023
- Phase
- Phase 1/2
- 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 2 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Ages 2-25 years.
- Participants (or their parents/legally-authorized representative) must provide signed informed consent.
- Assent must be obtained from those participants ages 7-17 years who are intellectually capable of understanding this study.
- Diagnosis of SLOS based on clinical features and biochemical + genetic confirmation.
- Participants are capable of traveling to the STAIR study site.
- Fasting plasma cholesterol ≤125 mg/dL during the Qualification Phase must be established before starting cholic acid therapy.
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- Clinically stable at the time of enrollment
- Participants must be on a constant dietary cholesterol intake for at least 3-months prior to treatment with cholic acid.
- Participants must agree to make no changes in cholesterol supplementation during the STAIR study.
- SLOS participants who are taking antioxidants will be included. Participants must agree to make no changes in the antioxidant dose during this study.
- For females of childbearing age (who have begun menstruating), a negative pregnancy test must be documented at the start of the study (week 0/ baseline) and at the end of cholic acid administration (week 8).
Who cannot join
- Participants are unable to provide signed informed consent and/or verbal assent.
- Participants have an unstable clinical condition that would prevent completion of the study. Medically unstable participants would include those with severe liver disease, complex birth defects such as severe heart disease or renal dysplasia, those with severe respiratory compromise requiring tracheostomy, or those who are not likely to survive longer than 1 year.
- Participants are taking drugs, nutraceuticals, probiotics or other compounds that are known or suspected to affect sterol metabolism.
- Participants have transaminase elevations (>3-fold above the reference range) at baseline.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Colorado Children's Hospital
Aurora, Colorado, 80045
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: Smith-Lemli-Opitz Syndrome: A Pilot Study of Cholic Acid Supplementation
The purpose of this study is to determine whether dietary cholic acid therapy benefits people with Smith-Lemli-Opitz syndrome (SLOS) by leading to an increase in plasma cholesterol and reduction in harmful cholesterol precursors. SLOS participants will be treated with dietary cholic acid for 8 weeks and plasma cholesterol and cholesterol precursor metabolites will be measured.
Read the detailed description
People with SLOS have a deficiency of the 7-dehydrocholesterol reductase enzyme that makes cholesterol. Consequently, they exhibit deficient cholesterol levels and increased cholesterol precursor lipids, which are thought to be toxic. Cholesterol itself normally regulates the cholesterol synthesis pathway in the body and under conditions of low cholesterol seen in SLOS, more of the toxic cholesterol precursors are made. Since cholesterol is also necessary for production of bile acids in the liver, which help digest dietary cholesterol from the intestine, it is likely that low cholesterol levels in SLOS impairs bile acids from being made, which in turn prevents dietary cholesterol from being absorbed properly and contributes to the cholesterol deficiency seen in SLOS. Raising cholesterol in SLOS people by improving its absorption from the diet is expected to decrease the potentially toxic cholesterol precursor lipids, and both changes would be theoretically beneficial for SLOS people.
The objective of this study is to determine whether treatment with cholic acid (a major bile acid made in the body that improves fat absorption) will increase dietary absorption of cholesterol, reverse plasma cholesterol deficiency, and reduce harmful cholesterol precursor lipids. These changes would be favorable for SLOS people. To accomplish this objective, SLOS participants will be given dietary cholic acid (brand name Cholbam, manufactured by Retrophin) for 8 weeks and plasma cholesterol and its precursor lipids will be measured before and while taking the drug.
SLOS participants who are between 2 years and 25 years of age and are taking supplemental dietary cholesterol for at least 3 months will be enrolled. Participants must be clinically stable and able to travel to a study site. No change in supplemental dietary cholesterol intake will be allowed during the study, and dietary records will be obtained throughout the study.
To qualify for cholic acid therapy, participants must have plasma cholesterol ≤125 mg/dl before starting cholic acid. Participants will be treated with cholic acid for 8 weeks and will have blood specimens drawn at baseline (day 0), 4-weeks, 8-weeks and 12 weeks (4 weeks after stopping cholic acid therapy).
- Conditions
- Smith-Lemli-Opitz Syndrome
- Being tested
- Cholic Acid
- Keywords
- 7-Dehydrocholesterol reductase deficiency
- Medical subject headings
- Smith-Lemli-Opitz Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cholic AcidDrug
Also called Cholbam
Participants will be treated with cholic acid for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Cholic acid | Experimental | Participants will be treated with cholic acid 10 mg/kg body weight. Receives: Drug: Cholic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Plasma Cholesterol
Plasma cholesterol will be measured. Response to cholic acid treatment will consist of a change in plasma cholesterol.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2018
- Study start27 Mar 2021
- Primary completion30 Aug 2022
- Study completion30 Sep 2023
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.
- Other trials for Smith-Lemli-Opitz SyndromeStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- University of Colorado, Denver, Children's Hospital Medical Center, Cincinnati, University of Pittsburgh
- Responsible party
- Sponsor
- Investigators
- Ellen R Elias, MD, Study chair, University of Colorado - Colorado Children's HospitalWilliam B Rizzo, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03720990
- Sponsor's protocol ID
- 0464-18-FB
- Status last verified
- Apr 2024
- First submitted
- 24 Oct 2018
- Last updated
- 30 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All data will be de-identified and submitted to the Database of Genotypes and Phenotypes (dbGAP), according to NIH regulations.
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Smith-Lemli-Opitz Syndrome: A Pilot Study of Cholic Acid Supplementation
- ClinicalTrials.gov ID
- NCT03720990
- Acronym / sponsor ID
- 0464-18-FB
- Conditions
- Smith-Lemli-Opitz Syndrome
- Keywords
- 7-Dehydrocholesterol reductase deficiency
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- University of Colorado, Denver, Children's Hospital Medical Center, Cincinnati, University of Pittsburgh
- Study start
- 27 Mar 2021 (actual)
- Primary completion
- 30 Aug 2022 (actual)
- Study completion
- 30 Sep 2023 (actual)
- First posted
- 26 Oct 2018 (actual)
- Results
- Posted 13 Dec 2023
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 study is to determine whether dietary cholic acid therapy benefits people with Smith-Lemli-Opitz syndrome (SLOS) by leading to an increase in plasma cholesterol and reduction in harmful cholesterol precursors. SLOS participants will be treated with dietary cholic acid for 8 weeks and plasma cholesterol and cholesterol precursor metabolites will be measured.
Detailed description
People with SLOS have a deficiency of the 7-dehydrocholesterol reductase enzyme that makes cholesterol. Consequently, they exhibit deficient cholesterol levels and increased cholesterol precursor lipids, which are thought to be toxic. Cholesterol itself normally regulates the cholesterol synthesis pathway in the body and under conditions of low cholesterol seen in SLOS, more of the toxic cholesterol precursors are made. Since cholesterol is also necessary for production of bile acids in the liver, which help digest dietary cholesterol from the intestine, it is likely that low cholesterol levels in SLOS impairs bile acids from being made, which in turn prevents dietary cholesterol from being absorbed properly and contributes to the cholesterol deficiency seen in SLOS. Raising cholesterol in SLOS people by improving its absorption from the diet is expected to decrease the potentially toxic cholesterol precursor lipids, and both changes would be theoretically beneficial for SLOS people.
The objective of this study is to determine whether treatment with cholic acid (a major bile acid made in the body that improves fat absorption) will increase dietary absorption of cholesterol, reverse plasma cholesterol deficiency, and reduce harmful cholesterol precursor lipids. These changes would be favorable for SLOS people. To accomplish this objective, SLOS participants will be given dietary cholic acid (brand name Cholbam, manufactured by Retrophin) for 8 weeks and plasma cholesterol and its precursor lipids will be measured before and while taking the drug.
SLOS participants who are between 2 years and 25 years of age and are taking supplemental dietary cholesterol for at least 3 months will be enrolled. Participants must be clinically stable and able to travel to a study site. No change in supplemental dietary cholesterol intake will be allowed during the study, and dietary records will be obtained throughout the study.
To qualify for cholic acid therapy, participants must have plasma cholesterol ≤125 mg/dl before starting cholic acid. Participants will be treated with cholic acid for 8 weeks and will have blood specimens drawn at baseline (day 0), 4-weeks, 8-weeks and 12 weeks (4 weeks after stopping cholic acid therapy).
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 | Experimental | Drug: Cholic AcidParticipants will be treated with cholic acid 10 mg/kg body weight. |
Who may qualify
- Ages
- 2 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- Ages 2-25 years.
- Participants (or their parents/legally-authorized representative) must provide signed informed consent.
- Assent must be obtained from those participants ages 7-17 years who are intellectually capable of understanding this study.
- Diagnosis of SLOS based on clinical features and biochemical + genetic confirmation.
- Participants are capable of traveling to the STAIR study site.
Key exclusion criteria (4 listed)
- Participants are unable to provide signed informed consent and/or verbal assent.
- Participants have an unstable clinical condition that would prevent completion of the study. Medically unstable participants would include those with severe liver disease, complex birth defects such as severe heart disease or renal dysplasia, those with severe respiratory compromise requiring tracheostomy, or those who are not likely to survive longer than 1 year.
- Participants are taking drugs, nutraceuticals, probiotics or other compounds that are known or suspected to affect sterol metabolism.
- Participants have transaminase elevations (>3-fold above the reference range) at baseline.
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 AcidAlso: CholbamParticipants will be treated with cholic acid for 8 weeks | Drug | Cholic acid |
Primary outcome
Change in Plasma Cholesterol
Time frame: 8 weeks
Plasma cholesterol will be measured. Response to cholic acid treatment will consist of a change in plasma cholesterol.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. All data will be de-identified and submitted to the Database of Genotypes and Phenotypes (dbGAP), according to NIH regulations.
Related trials for Smith-Lemli-Opitz Syndrome
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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.
Ellen R Elias, MD study chair
University of Colorado - Colorado Children's Hospital
William B Rizzo, MD principal investigator
University of Nebraska
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cholic Acid in people with Smith-Lemli-Opitz Syndrome, run by University of Nebraska at 2 sites 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 11 inclusion and 4 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 30 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 13 Dec 2023). 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?
Change in Plasma Cholesterol (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Apr 2024.