Clinical trial NCT01773278: Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
Official title: Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Smith-Lemli-Opitz Syndrome
Cone-Rod Dystrophy
Hearing Loss
Keywords: Antioxidant treatment
Oxysterols
Cholesterol deficiency
Accumulation of 7-dehydrocholesterol
electroretinogram (ERG)
Auditory Brainstem Response (ABR)
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2013-01-23
Enrollment: 100
Sex: ALL
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Change in Electroretinogram (ERG) results over time
timeFrame: 1-2 year
Secondary outcomes:
measure: Change in ABR (Auditory Brainstem response) testing over time
timeFrame: 1-2 years
Other outcomes:
measure: Change in Blood Oxysterol measurements over time
timeFrame: 12-24 months
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Ellen R Elias, MD
role: PRINCIPAL_INVESTIGATOR
References: