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

Purpose

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	Intervention
Smith-Lemli-Opitz Syndrome Cone-Rod Dystrophy Hearing Loss	Drug: Antioxidants Drug: Cholesterol

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease Farber lipogranulomatosis Lenz microphthalmia syndrome nonsyndromic deafness oculofaciocardiodental syndrome Pendred syndrome Peters plus syndrome retinitis pigmentosa Smith-Lemli-Opitz syndrome X-linked juvenile retinoschisis

MedlinePlus related topics: Antioxidants Cholesterol Hearing Disorders and Deafness Retinal Disorders

U.S. FDA Resources

Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:

Electroretinogram (ERG) testing [ Time Frame: 12 months ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

ABR (Auditory Brainstem response) testing [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Patients will be followed annually with ABR to determine the latency time in Wave I, when treated with antioxidant medication

Other Outcome Measures:

Blood Oxysterol measurements [ Time Frame: Every 4-6 months ] [ Designated as safety issue: No ]
Oxysterols can be measured in blood specimens from SLOS patients.

Estimated Enrollment:	30
Study Start Date:	December 2008
Estimated Study Completion Date:	December 2017
Estimated Primary Completion Date:	December 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 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 Name: AquADEKS 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 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 Name: AquADEKS 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 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 Name: AquADEKS 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

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:

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 starting, in collaboration with a laboratory at Vanderbilt University (Dr Ned Porter and Dr Libin Xu). It is hoped that testing of oxysterol levels in blood may help provide more updated info to help guide treatment.
New data is available and has been recently re-analyzed by a CTRC statistician, showing that the antioxidant treatment leads to statistically significant improvement in retinal function in SLOS patients, as measured on serial electroretinogram testing.

Eligibility

Ages Eligible for Study:	up to 65 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01773278

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

Sponsors and Collaborators

University of Colorado, Denver

Investigators

Principal Investigator:

Ellen R Elias, MD

University of Colorado, Denver

More Information

No publications provided

Responsible Party:	University of Colorado, Denver
ClinicalTrials.gov Identifier:	NCT01773278 History of Changes
Other Study ID Numbers:	01-0410
Study First Received:	December 3, 2012
Last Updated:	January 25, 2013
Health Authority:	United States: Institutional Review Board

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:

Antioxidants
Hearing Loss
Deafness
Retinitis Pigmentosa
Smith-Lemli-Opitz Syndrome
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Eye Diseases, Hereditary
Eye Diseases
Retinal Dystrophies

Retinal Degeneration
Retinal Diseases
Genetic Diseases, Inborn
Abnormalities, Multiple
Congenital Abnormalities
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Steroid Metabolism, Inborn Errors
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 23, 2013