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

NCT01773278 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 01-410
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change in ABR (Auditory Brainstem response) testing over time

  1-2 years

Other Outcomes (1)

• Change in Blood Oxysterol measurements over time

  12-24 months

Study Arms (3)

antioxidant effects on retinal function

EXPERIMENTAL

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; Drug: Cholesterol

antioxidant effects on hearing

EXPERIMENTAL

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

Drug: Antioxidants; Drug: Cholesterol

Antioxidant effect on Oxysterols

EXPERIMENTAL

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; Drug: Cholesterol

Interventions

Antioxidants 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.

Also known as: DEKAS Plus

Antioxidant effect on Oxysterols; antioxidant effects on hearing; antioxidant effects on retinal function

Cholesterol DRUG

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

Also known as: cholesterol suspension, eggs, Slo-lesterol

Antioxidant effect on Oxysterols; antioxidant effects on hearing; antioxidant effects on retinal function

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• absence of detectable 7-dehydrocholesterol/8-dehydrocholesterol
• allergy to Antioxidant medication

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

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

Interventions

Antioxidants; Cholesterol; Eggs

Condition Hierarchy (Ancestors)

Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Eye Diseases, Hereditary; Eye Diseases; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Factors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Protective Agents; Physiological Effects of Drugs; Specialty Uses of Chemicals; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Membrane Lipids; Lipids; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Ellen R Elias, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ellen R Elias, MD

CONTACT

720 777-5401; ellen.elias@childrenscolorado.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2012
• First Posted: January 23, 2013
• Study Start: December 1, 2008
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)