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

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.

Study Overview

• Status: Recruiting
• Conditions: Hearing Loss; Smith-Lemli-Opitz Syndrome; Cone-Rod Dystrophy
• Intervention / Treatment: Drug: Antioxidants; Drug: Cholesterol

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ellen R Elias, MD; Phone Number: 720 777-5401; Email: ellen.elias@childrenscolorado.org

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado
      • Principal Investigator: Ellen R Elias, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	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.; Other Names: DEKAS Plus; 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; Other Names: cholesterol suspension; eggs; Slo-lesterol
Experimental: 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)	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.; Other Names: DEKAS Plus; 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; Other Names: cholesterol suspension; eggs; Slo-lesterol
Experimental: 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	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.; Other Names: DEKAS Plus; 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; Other Names: cholesterol suspension; eggs; Slo-lesterol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Electroretinogram (ERG) results over time	ERG testing will be performed on an serial 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.	1-2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ABR (Auditory Brainstem response) testing over time	Patients will be followed serial with ABR to determine the latency time in Wave I, when treated with antioxidant medication	1-2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Blood Oxysterol measurements over time	Oxysterols can be measured in blood specimens from SLOS patients.	12-24 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Ellen R Elias, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: December 3, 2012
• First Submitted That Met QC Criteria: January 17, 2013
• First Posted (Estimated): January 23, 2013

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Antioxidant treatment; Oxysterols; Cholesterol deficiency; Accumulation of 7-dehydrocholesterol; electroretinogram (ERG); Auditory Brainstem Response (ABR)
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Disease; Urogenital Abnormalities; Congenital Abnormalities; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Mouth Diseases; Ear Diseases; Eye Diseases, Hereditary; Retinal Dystrophies; Bone Diseases; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Dyslipidemias; Sensation Disorders; Mouth Abnormalities; Stomatognathic System Abnormalities; Jaw Abnormalities; Jaw Diseases; Maxillofacial Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Abnormalities, Multiple; Hearing Disorders; Lipid Metabolism, Inborn Errors; Bone Diseases, Developmental; Steroid Metabolism, Inborn Errors; Penile Diseases; Craniofacial Dysostosis; Dysostoses; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Syndrome; Cleft Palate; Hearing Loss; Cone-Rod Dystrophies; Hypospadias; Genetic Diseases, X-Linked; Smith-Lemli-Opitz Syndrome; Hypertelorism; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants
• Other Study ID Numbers: 01-410

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No