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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Smith-Lemli-Opitz Syndrome; Cone-Rod Dystrophy; Hearing Loss	Drug: Antioxidants; Drug: Cholesterol	Phase 2

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. 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	100 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
Study Start Date :	December 2008
Estimated Primary Completion Date :	December 2018
Estimated Study Completion Date :	December 2018

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 AquADEKS or DEKAs 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.; Other Names: AquADEKS; DEKAs 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 AquADEKS or DEKAs 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.; Other Names: AquADEKS; DEKAs 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 AquADEKS or DEKAs 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.; Other Names: AquADEKS; DEKAs 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

Outcome Measures

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Primary Outcome Measures :

1. Change in Electroretinogram (ERG) results over time [ Time Frame: 1-2 year ]
   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.

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Change in Blood Oxysterol measurements over time [ Time Frame: 12-24 months ]
   Oxysterols can be measured in blood specimens from SLOS patients.

Eligibility Criteria

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Ages Eligible for Study:	up to 65 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Ellen R Elias, MD	720 777-5401	ellen.elias@childrenscolorado.org

Locations

United States, Colorado
Children's Hospital Colorado	Recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Ellen R Elias, MD
Sub-Investigator: Rebecca S Braverman, MD
Sub-Investigator: Chun-hui Tsai, MD

Sponsors and Collaborators

University of Colorado, Denver

Investigators

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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	University of Colorado, Denver
ClinicalTrials.gov Identifier:	NCT01773278 History of Changes
Other Study ID Numbers:	01-410
First Posted:	January 23, 2013
Last Update Posted:	August 29, 2017
Last Verified:	August 2017

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by University of Colorado, Denver:

Antioxidant treatment; Oxysterols; Cholesterol deficiency	Accumulation of 7-dehydrocholesterol; electroretinogram (ERG); Auditory Brainstem Response (ABR)

Additional relevant MeSH terms:

Syndrome; Hearing Loss; Cleft Palate; Hypertelorism; Hypospadias; Genetic Diseases, X-Linked; Smith-Lemli-Opitz Syndrome; Cone-Rod Dystrophies; Retinitis Pigmentosa; Disease; Pathologic Processes; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders	Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Jaw Abnormalities; Jaw Diseases; Musculoskeletal Diseases; Maxillofacial Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Stomatognathic Diseases; Mouth Abnormalities; Mouth Diseases; Stomatognathic System Abnormalities; Congenital Abnormalities; Craniofacial Dysostosis