SLOS: The Effect of Simvastatin in Patients Receiving Cholesterol Supplementation
Primary Purpose
Smith-Lemli-Opitz Syndrome
Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Simvastatin
Lactose
Sponsored by
About this trial
This is an interventional treatment trial for Smith-Lemli-Opitz Syndrome focused on measuring SLOS, Cholesterol Supplementation, Simvastatin
Eligibility Criteria
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
Sites / Locations
- Oregon Health and Science University
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Simvastatin
Arm Description
placebo
0.5 mg/kg body weight/day
Outcomes
Primary Outcome Measures
Development Quotient (DQ)
neurocognitive assessment measured with Mullen Scales of Learning
Secondary Outcome Measures
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
Plasma Marker of Sterol Metabolism
Blood cholesterol to 7-dehydrocholesterol ratio
ADC
Apparent diffusion coefficient measured by brain diffusion tensor imaging (DTI)
MVA
urinary mevalonate excretion
MRS Lipids
Brain magnetic resonance spectroscopy
FA
Fractional anisotropy as measured by brain diffusion tensor imaging (DTI)
Full Information
NCT ID
NCT01434745
First Posted
September 7, 2011
Last Updated
September 12, 2019
Sponsor
Oregon Health and Science University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT01434745
Brief Title
SLOS: The Effect of Simvastatin in Patients Receiving Cholesterol Supplementation
Official Title
Smith-Lemli Opitz Syndrome: A Clinical Investigation of the Effect of Simvastatin in Patients Receiving Cholesterol Supplementation
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Terminated
Why Stopped
poor enrollment (only one subject enrolled)
Study Start Date
September 2011 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oregon Health and Science University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Smith-Lemli-Opitz Syndrome
Keywords
SLOS, Cholesterol Supplementation, Simvastatin
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
placebo
Arm Title
Simvastatin
Arm Type
Experimental
Arm Description
0.5 mg/kg body weight/day
Intervention Type
Drug
Intervention Name(s)
Simvastatin
Other Intervention Name(s)
Zocor, Flolipid
Intervention Description
Simvastatin will be administered as a powder mixed with lactose at the dose of 0.5 mg/kg/day
Intervention Type
Dietary Supplement
Intervention Name(s)
Lactose
Intervention Description
Lactose will be administered in a capsule formula.
Primary Outcome Measure Information:
Title
Development Quotient (DQ)
Description
neurocognitive assessment measured with Mullen Scales of Learning
Time Frame
through study completion, an average of 2 per year
Secondary Outcome Measure Information:
Title
Whole Body Cholesterol Pool Size, Synthesis & Absorption Using Stable Isotope Testing
Description
administration of cholesterol and water labeled with stable isotope followed by measurement overtime in blood concentrations
Time Frame
end of treatment, an average of 1 per year
Title
Plasma Marker of Sterol Metabolism
Description
Blood cholesterol to 7-dehydrocholesterol ratio
Time Frame
through study completion, an average of 2 per year
Title
ADC
Description
Apparent diffusion coefficient measured by brain diffusion tensor imaging (DTI)
Time Frame
end of treatment, an average of 1 per year
Title
MVA
Description
urinary mevalonate excretion
Time Frame
through study completion, an average of 2 per year
Title
MRS Lipids
Description
Brain magnetic resonance spectroscopy
Time Frame
end of treatment, an average of 1 per year
Title
FA
Description
Fractional anisotropy as measured by brain diffusion tensor imaging (DTI)
Time Frame
end of treatment, an average of 1 per year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Baptiste Roullet, PhD
Organizational Affiliation
Washington State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
12. IPD Sharing Statement
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SLOS: The Effect of Simvastatin in Patients Receiving Cholesterol Supplementation
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