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

Hearing Loss Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01773278
• Other study ID #: 01-410
• Status: Recruiting
• Phase: Phase 2
• Start date: December 2008
• Est. completion date: December 2025

Study information

• Verified date: May 2024
• Source: University of Colorado, Denver
• Contact: Ellen R Elias, MD
• Phone: 720 777-5401
• Email: ellen.elias[@]childrenscolorado.org
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Cleft Palate
• Cone-Rod Dystrophy
• Genetic Diseases, X-Linked
• Hearing Loss
• Hypospadias
• Smith-Lemli-Opitz Syndrome
• Syndrome

Intervention

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.
• Cholesterol
Patients with SLOS typically have cholesterol deficiency. They will be treated with cholesterol supplementation to keep cholesterol levels > 100 mg/dl if possible

Locations

Country	Name	City	State
United States	Children's Hospital Colorado	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Blood Oxysterol measurements over time	Oxysterols can be measured in blood specimens from SLOS patients.	12-24 months
Primary	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.	1-2 year
Secondary	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	1-2 years