SLOS: The Effect of Simvastatin in Patients Receiving Cholesterol Supplementation

Not Applicable

Terminated

• Conditions: Smith-Lemli-Opitz Syndrome
• Interventions: Dietary Supplement: Lactose; Drug: Simvastatin

• Registration Number: NCT01434745
• Lead Sponsor: Oregon Health and Science University

Brief Summary

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

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.

Study Timeline

• Study Start: 2011-09
• Study First Submitted: 2011-09-07
• Study First Submitted QC: 2011-09-13
• Study First Posted: 2011-09-15
• Primary Completion: 2014-10
• Study Completion: 2014-10
• Status Verified: 2019-09
• Results First Submitted: 2019-09-12
• Results First Submitted QC: 2019-09-12
• Last Update Submitted: 2019-09-12
• Results First Posted: 2019-10-01
• Last Update Posted: 2019-10-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Lactose	placebo
Simvastatin	Simvastatin	0.5 mg/kg body weight/day

Primary Outcome Measures

Name	Time	Method
Development Quotient (DQ)	through study completion, an average of 2 per year	neurocognitive assessment measured with Mullen Scales of Learning

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States