NCT01773278

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: University of Colorado, Denver · Academic / Other
• Sex: All
• Age: 65 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Smith-Lemli-Opitz Syndrome
• Cone-Rod Dystrophy
• Hearing Loss

Interventions

Type	Name	Description
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.
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

Timeline

• Start date: 2008-12-01
• Primary completion: 2025-12-01
• Completion: 2025-12-01
• First posted: 2013-01-23
• Last updated: 2024-05-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study