Trial record 5 of 5 for:    "Brainstem auditory evoked responses"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of Colorado, Denver
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01773278
First received: December 3, 2012
Last updated: January 25, 2013
Last verified: January 2013
  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:


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:

  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 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.
  2. 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Cleft Palate
Deafness
Genetic Diseases, X-Linked
Hearing Loss
Hypertelorism
Hypospadias
Retinitis Pigmentosa
Smith-Lemli-Opitz Syndrome
Syndrome
Abnormalities, Multiple
Bone Diseases
Bone Diseases, Developmental
Congenital Abnormalities
Craniofacial Abnormalities
Craniofacial Dysostosis
Disease
Dyslipidemias
Dysostoses
Ear Diseases
Eye Diseases
Eye Diseases, Hereditary
Genetic Diseases, Inborn
Genital Diseases, Male
Hearing Disorders
Jaw Abnormalities
Jaw Diseases
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Maxillofacial Abnormalities
Metabolic Diseases

ClinicalTrials.gov processed this record on October 29, 2014