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

NCT ID: NCT01773278

Last Updated: 2024-05-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2025-12-31

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

antioxidant effects on retinal function

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

Group Type: EXPERIMENTAL

Antioxidants

Intervention Type: DRUG

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

Intervention Type: DRUG

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

antioxidant effects on hearing

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

Group Type: EXPERIMENTAL

Antioxidants

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Antioxidant effect on Oxysterols

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

Group Type: EXPERIMENTAL

Antioxidants

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

DEKAS Plus; cholesterol suspension; eggs; Slo-lesterol

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

• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ellen R Elias, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ellen R Elias, MD

Role: CONTACT

ellen.elias@childrenscolorado.org

720 777-5401

Other Identifiers

01-410

Identifier Type: -

Identifier Source: org_study_id