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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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 an annual basis, 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 Summary:

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. Since 2008, a second medication called AquADEKS, a mixture of vitamins and other compounds with antioxidant properties was added to the treatment regimen. The purpose of the AquADEKS 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. Since the last Colorado Multiple Institutional Review Board annual review, the following updated information is available about the protocol:

1. New research has revealed that oxysterols are toxic compounds made from the cholesterol precursor, 7-dehydrocholesterol. These oxysterol compounds are severely neurotoxic 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 Vanderbilt University (Dr Ned Porter). It is hoped that testing of oxysterol levels in blood may help provide more updated info to help guide treatment.


Sponsor: University of Colorado, Denver

Current Primary Outcome: Electroretinogram (ERG) testing [ Time Frame: 12 months ]

ERG testing will be performed on an annual 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.


Original Primary Outcome: Same as current

Current Secondary Outcome: ABR (Auditory Brainstem response) testing [ Time Frame: 12 months ]

Patients will be followed annually with ABR to determine the latency time in Wave I, when treated with antioxidant medication


Original Secondary Outcome: Same as current

Information By: University of Colorado, Denver

Dates:
Date Received: December 3, 2012
Date Started: December 2008
Date Completion: December 2018
Last Updated: August 18, 2016
Last Verified: August 2016