SLOS: The Effect of Simvastatin in Patients Receiving Cholesterol Supplementation

Study Overview
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Brief Summary
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The purpose of this study is to determine if simvastatin improves development and behavior in patients with Smith Lemli-Opitz syndrome (SLOS) receiving dietary cholesterol supplementation.

Detailed Description
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Patients with SLOS receiving dietary cholesterol supplementation are given simvastatin, a drug that decreases the activity/expression of HMG-CoA reductase, an enzyme that controls the first step of the cholesterol synthesis pathway, reduces the accumulation of toxic 7-dehydrocholesterol (immediate metabolic precursor of cholesterol) and improve neurocognitive and behavioral outcomes.

Official Title
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Smith-Lemli Opitz Syndrome: A Clinical Investigation of the Effect of Simvastatin in Patients Receiving Cholesterol Supplementation

Conditions
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Smith-Lemli-Opitz Syndrome

Intervention / Treatment
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* Drug: Simvastatin
* Dietary Supplement: Lactose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female over 1 years old Subject has confirmed diagnosis of Smith-Lemli-Opitz Syndrome Subject is currently receiving cholesterol supplementation Exclusion Criteria: Subjects too ill to travel to the study site Subjects who are unable to safely undergo study procedures Pregnant women

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 89 Years

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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>placebo | Dietary Supplement: Lactose<br>* Lactose will be administered in a capsule formula.<br>|
| Experimental: Simvastatin<br>0.5 mg/kg body weight/day | Drug: Simvastatin<br>* Simvastatin will be administered as a powder mixed with lactose at the dose of 0.5 mg/kg/day<br>* Other names: Zocor, Flolipid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development Quotient (DQ) | neurocognitive assessment measured with Mullen Scales of Learning | through study completion, an average of 2 per year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole Body Cholesterol Pool Size, Synthesis & Absorption Using Stable Isotope Testing | administration of cholesterol and water labeled with stable isotope followed by measurement overtime in blood concentrations | end of treatment, an average of 1 per year | 
| Plasma Marker of Sterol Metabolism | Blood cholesterol to 7-dehydrocholesterol ratio | through study completion, an average of 2 per year | 
| ADC | Apparent diffusion coefficient measured by brain diffusion tensor imaging (DTI) | end of treatment, an average of 1 per year | 
| MVA | urinary mevalonate excretion | through study completion, an average of 2 per year | 
| MRS Lipids | Brain magnetic resonance spectroscopy | end of treatment, an average of 1 per year | 
| FA | Fractional anisotropy as measured by brain diffusion tensor imaging (DTI) | end of treatment, an average of 1 per year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLOS, Cholesterol Supplementation, Simvastatin