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Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)

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ClinicalTrials.gov Identifier: NCT01773278
Recruitment Status : Recruiting
First Posted : January 23, 2013
Last Update Posted : January 20, 2022
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Study Description
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Brief 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. 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.

Condition or disease Intervention/treatment Phase
Smith-Lemli-Opitz Syndrome Cone-Rod Dystrophy Hearing Loss Drug: Antioxidants Drug: Cholesterol Phase 2

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:

1. 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
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
Study Start Date : December 2008
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: antioxidant effects on retinal function
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
 Drug: Antioxidants
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.
Other Name: DEKAS Plus

Drug: Cholesterol
Patients with SLOS typically have cholesterol deficiency. They will be treated with cholesterol supplementation to keep cholesterol levels > 100 mg/dl if possible
Other Names:
  • cholesterol suspension
  • eggs
  • Slo-lesterol
Experimental: antioxidant effects on hearing
Patients with SLOS will be treated with cholesterol and antioxidant medication and their hearing will be followed by serial brainstem audiometry (ABR)
 Drug: Antioxidants
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.
Other Name: DEKAS Plus

Drug: Cholesterol
Patients with SLOS typically have cholesterol deficiency. They will be treated with cholesterol supplementation to keep cholesterol levels > 100 mg/dl if possible
Other Names:
  • cholesterol suspension
  • eggs
  • Slo-lesterol
Experimental: Antioxidant effect on Oxysterols
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
 Drug: Antioxidants
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.
Other Name: DEKAS Plus

Drug: Cholesterol
Patients with SLOS typically have cholesterol deficiency. They will be treated with cholesterol supplementation to keep cholesterol levels > 100 mg/dl if possible
Other Names:
  • cholesterol suspension
  • eggs
  • Slo-lesterol


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Change in ABR (Auditory Brainstem response) testing over time [ Time Frame: 1-2 years ]
    Patients will be followed serial with ABR to determine the latency time in Wave I, when treated with antioxidant medication


Other Outcome Measures:
  1. Change in Blood Oxysterol measurements over time [ Time Frame: 12-24 months ]
    Oxysterols can be measured in blood specimens from SLOS patients.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   up to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • absence of detectable 7-dehydrocholesterol/8-dehydrocholesterol
  • allergy to Antioxidant medication
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01773278


Contacts
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Contact: Ellen R Elias, MD 720 777-5401 ellen.elias@childrenscolorado.org

Locations
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United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Ellen R Elias, MD         
Sponsors and Collaborators
University of Colorado, Denver
Investigators
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Principal Investigator: Ellen R Elias, MD University of Colorado, Denver
More Information
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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01773278    
Other Study ID Numbers: 01-410
First Posted: January 23, 2013    Key Record Dates
Last Update Posted: January 20, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Colorado, Denver:
Antioxidant treatment
Oxysterols
Cholesterol deficiency
 Accumulation of 7-dehydrocholesterol
electroretinogram (ERG)
Auditory Brainstem Response (ABR)
Additional relevant MeSH terms:
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Cleft Palate
Hypertelorism
Hearing Loss
Cone-Rod Dystrophies
Hypospadias
Genetic Diseases, X-Linked
Smith-Lemli-Opitz Syndrome
Syndrome
Disease
Pathologic Processes
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
 Nervous System Diseases
Jaw Abnormalities
Jaw Diseases
Musculoskeletal Diseases
Maxillofacial Abnormalities
Craniofacial Abnormalities
Musculoskeletal Abnormalities
Stomatognathic Diseases
Mouth Abnormalities
Mouth Diseases
Stomatognathic System Abnormalities
Congenital Abnormalities
Craniofacial Dysostosis
Dysostoses
Bone Diseases, Developmental