Smith-Lemli-Opitz SyndromePhase 2NCT01773278
Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
A Phase 2 study testing Antioxidants and Cholesterol in people with Smith-Lemli-Opitz Syndrome and Cone-Rod Dystrophy, run by University of Colorado, Denver at 1 site in United States.
Trial summary
Patients with biochemically confirmed SLOS are being treated with cholesterol supplementation and antioxidant medication. They are carefully monitored with visits to clinic, laboratory testing including cholesterol and 7-dehydrocholesterol levels, vitamin levels, blood counts and liver and kidney function. Read more about this study
- Who is it for?
- Ages Up to 65 years
- Conditions the study is for
- Smith-Lemli-Opitz Syndrome, Cone-Rod Dystrophy, Hearing Loss
- What is being tested?
- Antioxidants and Cholesterol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2008to Dec 2025
- Phase
- Phase 2
- 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 Up to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Clinical diagnosis of Smith-Lemli-Opitz Syndrome
- Elevated levels of 7-dehydrocholesterol and 8-dehydrocholesterol
- Must be able to travel to Children's Hospital Colorado annually
- Must have insurance coverage for ERG/ABR studies
Who cannot join
- absence of detectable 7-dehydrocholesterol/8-dehydrocholesterol
- allergy to Antioxidant medication
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
Ellen R Elias, MD
About this study
Patients with biochemically confirmed SLOS are being treated with cholesterol supplementation and antioxidant medication. They are carefully monitored with visits to clinic, laboratory testing including cholesterol and 7-dehydrocholesterol levels, vitamin levels, blood counts and liver and kidney function. On a serial basis, no more often than once a year, the patients undergo a series of tests under anesthesia, including electroretinogram (ERG), brainstem audiometry (ABR), and ophthalmologic exam under anesthesia to follow pigmentary retinopathy.
Read the detailed description
Smith-Lemli-Opitz Syndrome (SLOS) is an autosomal recessive disorder caused by a metabolic error in the final step of cholesterol biosynthesis, leading to cholesterol deficiency and accumulation of the cholesterol precursor, 7-dehydrocholesterol.Patients with SLOS display complex medical problems including growth failure, intellectual disability, behavioral disorders, progressive retinal dystrophy, hearing loss and photosensitivity. Dr Elias was one of the original geneticists who discovered the cause of this disorder in 1994, and ever since has been treating SLOS patients with cholesterol supplementation. In 2008, a second medication called AquADEKS, a mixture of vitamins and other compounds with antioxidant properties was added to the treatment regimen. AquADEKS has since been replaced with a comparable medication named DEKAS plus.The purpose of the DEKAS plus is to allow treatment with antioxidant medications in an effort to prevent retinal degeneration, hearing and skin problems associated with SLOS.
This protocol has been approved by the Colorado Multiple Institutional Review Board and supported by the Clinical Translational Research Center (CTRC) since 2001. The following updated information is available about the protocol:
- Research has revealed that oxysterols are toxic compounds made from the cholesterol precursor, 7-dehydrocholesterol. These oxysterol compounds are severely neurotoxic and toxic to the retina, and treatment with antioxidants may help lower their levels, resulting in slowing of retinal deterioration. Testing of oxysterol levels in patients with SLOS is now ongoing, in collaboration with a laboratory at University of Washington in Seattle (Dr Libin Xu). It is hoped that testing of oxysterol levels in blood may help provide more updated info to help guide treatment.
- Conditions
- Smith-Lemli-Opitz Syndrome, Cone-Rod Dystrophy, Hearing Loss
- Being tested
- Antioxidants, Cholesterol
- Keywords
- Antioxidant treatment, Oxysterols, Cholesterol deficiency, Accumulation of 7-dehydrocholesterol, electroretinogram (ERG), Auditory Brainstem Response (ABR)
- Medical subject headings
- Smith-Lemli-Opitz Syndrome, Cone-Rod Dystrophies, Hearing Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AntioxidantsDrug
Also called DEKAS Plus
Patients will be prescribed the drug DEKAS plus at a dose based on age and weight. The effects of the treatment will be monitored by serial ERG, ABR, oxysterol levels and clinical findings. Blood levels of 25-Oh vitamin D will be monitored to prevent toxicity.
CholesterolDrug
Also called cholesterol suspension, eggs, Slo-lesterol
Patients with SLOS typically have cholesterol deficiency. They will be treated with cholesterol supplementation to keep cholesterol levels > 100 mg/dl if possible
| Study group | Role | What they receive |
|---|---|---|
| antioxidant effects on retinal function | Experimental | Patients with SLOS will be treated with both cholesterol supplementation and antioxidants. Retinal function will be followed by serial electroretinogram (ERG) testing and pigmentary retinopathy will be followed by Serial Ophthalmologic exams under anesthesia Receives: Drug: Antioxidants; Drug: Cholesterol |
| antioxidant effects on hearing | Experimental | Patients with SLOS will be treated with cholesterol and antioxidant medication and their hearing will be followed by serial brainstem audiometry (ABR) Receives: Drug: Antioxidants; Drug: Cholesterol |
| Antioxidant effect on Oxysterols | Experimental | Patients with SLOS will be treated with antioxidants and cholesterol. Blood oxysterol levels will be measured. Future focus will be on being able to use oxysterol levels to regulate antioxidant doses, and to determine which particular antioxidants might have the most benefit in lowering oxysterols Receives: Drug: Antioxidants; Drug: Cholesterol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Electroretinogram (ERG) results over time
ERG testing will be performed on an serial basis while the patient is being treated with antioxidants (AquADEKS), to follow the amplitude and latency time on ERG. Improvement would be determined by an increased amplitude and decreased latency time.
Measured: 1-2 year
Secondary outcomes (1)
Change in ABR (Auditory Brainstem response) testing over time
Patients will be followed serial with ABR to determine the latency time in Wave I, when treated with antioxidant medication
Measured: 1-2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2013 (estimated)
- Study startDec 2008
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Smith-Lemli-Opitz SyndromeStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ellen R Elias, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01773278
- Sponsor's protocol ID
- 01-410
- Status last verified
- May 2024
- First submitted
- 3 Dec 2012
- Last updated
- 8 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
- ClinicalTrials.gov ID
- NCT01773278
- Acronym / sponsor ID
- 01-410
- Conditions
- Smith-Lemli-Opitz Syndrome, Cone-Rod Dystrophy, Hearing Loss
- Keywords
- Antioxidant treatment, Oxysterols, Cholesterol deficiency, Accumulation of 7-dehydrocholesterol, electroretinogram (ERG), Auditory Brainstem Response (ABR)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- Dec 2008
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 23 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with biochemically confirmed SLOS are being treated with cholesterol supplementation and antioxidant medication. They are carefully monitored with visits to clinic, laboratory testing including cholesterol and 7-dehydrocholesterol levels, vitamin levels, blood counts and liver and kidney function. On a serial basis, no more often than once a year, the patients undergo a series of tests under anesthesia, including electroretinogram (ERG), brainstem audiometry (ABR), and ophthalmologic exam under anesthesia to follow pigmentary retinopathy.
Detailed description
Smith-Lemli-Opitz Syndrome (SLOS) is an autosomal recessive disorder caused by a metabolic error in the final step of cholesterol biosynthesis, leading to cholesterol deficiency and accumulation of the cholesterol precursor, 7-dehydrocholesterol.Patients with SLOS display complex medical problems including growth failure, intellectual disability, behavioral disorders, progressive retinal dystrophy, hearing loss and photosensitivity. Dr Elias was one of the original geneticists who discovered the cause of this disorder in 1994, and ever since has been treating SLOS patients with cholesterol supplementation. In 2008, a second medication called AquADEKS, a mixture of vitamins and other compounds with antioxidant properties was added to the treatment regimen. AquADEKS has since been replaced with a comparable medication named DEKAS plus.The purpose of the DEKAS plus is to allow treatment with antioxidant medications in an effort to prevent retinal degeneration, hearing and skin problems associated with SLOS.
This protocol has been approved by the Colorado Multiple Institutional Review Board and supported by the Clinical Translational Research Center (CTRC) since 2001. The following updated information is available about the protocol:
- Research has revealed that oxysterols are toxic compounds made from the cholesterol precursor, 7-dehydrocholesterol. These oxysterol compounds are severely neurotoxic and toxic to the retina, and treatment with antioxidants may help lower their levels, resulting in slowing of retinal deterioration. Testing of oxysterol levels in patients with SLOS is now ongoing, in collaboration with a laboratory at University of Washington in Seattle (Dr Libin Xu). It is hoped that testing of oxysterol levels in blood may help provide more updated info to help guide treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| antioxidant effects on retinal function | Experimental | Drug: Antioxidants, Drug: CholesterolPatients with SLOS will be treated with both cholesterol supplementation and antioxidants. Retinal function will be followed by serial electroretinogram (ERG) testing and pigmentary retinopathy will be followed by Serial Ophthalmologic exams under anesthesia |
| antioxidant effects on hearing | Experimental | Drug: Antioxidants, Drug: CholesterolPatients with SLOS will be treated with cholesterol and antioxidant medication and their hearing will be followed by serial brainstem audiometry (ABR) |
| Antioxidant effect on Oxysterols | Experimental | Drug: Antioxidants, Drug: CholesterolPatients with SLOS will be treated with antioxidants and cholesterol. Blood oxysterol levels will be measured. Future focus will be on being able to use oxysterol levels to regulate antioxidant doses, and to determine which particular antioxidants might have the most benefit in lowering oxysterols |
Who may qualify
- Ages
- Up to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Clinical diagnosis of Smith-Lemli-Opitz Syndrome
- Elevated levels of 7-dehydrocholesterol and 8-dehydrocholesterol
- Must be able to travel to Children's Hospital Colorado annually
- Must have insurance coverage for ERG/ABR studies
Key exclusion criteria (2 listed)
- absence of detectable 7-dehydrocholesterol/8-dehydrocholesterol
- allergy to Antioxidant medication
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 |
|---|---|---|
| AntioxidantsAlso: DEKAS PlusPatients will be prescribed the drug DEKAS plus at a dose based on age and weight. The effects of the treatment will be monitored by serial ERG, ABR, oxysterol levels and clinical findings. Blood levels of 25-Oh vitamin D will be monitored to prevent toxicity. | Drug | Antioxidant effect on Oxysterols, antioxidant effects on hearing, antioxidant effects on retinal function |
| CholesterolAlso: cholesterol suspension, eggs, Slo-lesterolPatients with SLOS typically have cholesterol deficiency. They will be treated with cholesterol supplementation to keep cholesterol levels > 100 mg/dl if possible | Drug | Antioxidant effect on Oxysterols, antioxidant effects on hearing, antioxidant effects on retinal function |
Primary outcome
Change in Electroretinogram (ERG) results over time
Time frame: 1-2 year
ERG testing will be performed on an serial basis while the patient is being treated with antioxidants (AquADEKS), to follow the amplitude and latency time on ERG. Improvement would be determined by an increased amplitude and decreased latency time.
1 secondary outcome
Change in ABR (Auditory Brainstem response) testing over time
Time frame: 1-2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
- Individual participant dataSharing planned: No
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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 principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Antioxidants and Cholesterol in people with Smith-Lemli-Opitz Syndrome and Cone-Rod Dystrophy, run by University of Colorado, Denver 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 2 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: status not confirmed, as of the sponsor's last update on 8 May 2024. 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ellen R Elias, MD (720 777-5401, ellen.elias@childrenscolorado.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Electroretinogram (ERG) results over time (time frame: 1-2 year). 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 8 May 2024.