Treatment of the Cholesterol Defect in Smith-Lemli-Opitz Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to determine whether supplementation with an oil-based cholesterol suspension will correct the biochemical abnormalities in cholesterol and its precursors in individuals with the Smith-Lemli-Opitz syndrome.

Detailed Description
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This study involves treating individuals with the Smith-Lemli-Opitz syndrome, a rare inborn error of cholesterol metabolism, with supplemental cholesterol to determine it effects on biochemical sterol metabolites, growth, neuropsychological development, ophthalmologic and auditory function, ERG (electroretinogram) parameters, and CNS metabolites as determined by brain MRS-imaging. Safety of the supplemental cholesterol suspension is monitored by tests of hematologic, renal, and liver function at periodic intervals. There is also a substudy that is investigating potential genotype-phenotype correlations, as well as another that studies biochemical parameters of light sensitivity in cultured skin fibroblasts from affected patients.

Official Title
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Treatment of the Cholesterol Defect in Smith-Lemli-Opitz Syndrome

Conditions
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Smith-Lemli-Opitz Syndrome

Intervention / Treatment
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* Drug: crystalline cholesterol oil-based suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biochemical confirmation of sterol defect associated with Smith-Lemli-Opitz syndrome Exclusion Criteria: Inability to tolerate crystalline cholesterol Inability to travel to Boston 3-4 times/year based on age
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cholesterol supplementation<br> | Drug: crystalline cholesterol oil-based suspension<br>* 200 mg/mL suspension of crystalline cholesterol in oil. Dosage (generally 75-300 mg/kg/day in divided doses) is based on initial cholesterol levels and regulated to increase, yet maintain, cholesterol levels no higher than normal ranges.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Responders | Responders was defined as an increase in total serum cholesterol and a decrease in 7-DHC (7-Dehydrocholesterol), and 8-DHC (8-Dehydrocholesterol) were measured on all participants. | Every 3-6 months for an approximate median of 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Growth Responders | Growth response was defined as an increase in general health, growth, and behavior. | Every 3-6 months for an approximate median of 5 years | 
| Number of Participants With Improved Neuropsychological Development | Improved neuropsychological development is defined as progressively achieving developmental milestones | Every 3-6 months for an approximate median of 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sterols, cholesterol, Smith-Lemli-Opitz syndrome, mental retardation, congenital anomalies