SLOS: The Effect of Simvastatin in Patients Receiving Cholesterol Supplementation

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

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.

Study Overview

• Status: Terminated
• Conditions: Smith-Lemli-Opitz Syndrome
• Intervention / Treatment: Dietary supplement: Lactose; Drug: Simvastatin

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 Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 89 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; placebo	Dietary supplement: Lactose; Lactose will be administered in a capsule formula.
EXPERIMENTAL: Simvastatin; 0.5 mg/kg body weight/day	Drug: Simvastatin; Simvastatin will be administered as a powder mixed with lactose at the dose of 0.5 mg/kg/day; Other Names: Zocor, Flolipid

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Jean-Baptiste Roullet, PhD, Washington State University

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: September 7, 2011
• First Submitted That Met QC Criteria: September 13, 2011
• First Posted (ESTIMATE): September 15, 2011

Study Record Updates

• Last Update Posted (ACTUAL): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 12, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Simvastatin; SLOS; Cholesterol Supplementation
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Dyslipidemias; Abnormalities, Multiple; Lipid Metabolism, Inborn Errors; Steroid Metabolism, Inborn Errors; Syndrome; Smith-Lemli-Opitz Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: R01HL073980 (NIH)