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

University of Colorado Denver (CU Denver)

Status and phase: Enrolling; Phase 2

Conditions: Smith-Lemli-Opitz Syndrome; Hearing Loss; Cone-Rod Dystrophy

Treatments: Drug: Cholesterol; Drug: Antioxidants

Study type: Interventional

Funder types: Other

Identifiers

NCT01773278

01-410

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: Under 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 3 patient groups

antioxidant effects on retinal function

Experimental group

Description:

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

Treatment:

Drug: Cholesterol

Drug: Antioxidants

antioxidant effects on hearing

Experimental group

Description:

Patients with SLOS will be treated with cholesterol and antioxidant medication and their hearing will be followed by serial brainstem audiometry (ABR)

Treatment:

Drug: Cholesterol

Drug: Antioxidants

Antioxidant effect on Oxysterols

Experimental group

Description:

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

Treatment:

Drug: Cholesterol

Drug: Antioxidants