Smith-Lemli-Opitz Syndrome
Conditions
Keywords
SLOS, Cholesterol Supplementation, Simvastatin
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.
Interventions
DRUGSimvastatin
Simvastatin will be administered as a powder mixed with lactose at the dose of 0.5 mg/kg/day
DIETARY_SUPPLEMENTLactose
Lactose will be administered in a capsule formula.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
1 Years to 89 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Development Quotient (DQ) | through study completion, an average of 2 per year | neurocognitive assessment measured with Mullen Scales of Learning |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Marker of Sterol Metabolism | through study completion, an average of 2 per year | Blood cholesterol to 7-dehydrocholesterol ratio |
| 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 |
| MRS Lipids | end of treatment, an average of 1 per year | Brain magnetic resonance spectroscopy |
| FA | end of treatment, an average of 1 per year | Fractional anisotropy as measured by brain diffusion tensor imaging (DTI) |
| MVA | through study completion, an average of 2 per year | urinary mevalonate excretion |
Countries
United States
Participant flow
Recruitment details
Only one participant enrolled
Participants by arm
| Arm | Count |
|---|---|
| Placebo - Lactose Placebo-Lactose
Lactose: Lactose will be administered in a capsule formula. | 0 |
| Simvastatin 0.5 mg/kg body weight/day
Simvastatin: Simvastatin will be administered as a powder mixed with lactose at the dose of 0.5 mg/kg/day | 0 |
| Total | 0 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Region of Enrollment United States | — participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Development Quotient (DQ)
neurocognitive assessment measured with Mullen Scales of Learning
Time frame: through study completion, an average of 2 per year
Population: No funding
Secondary
ADC
Apparent diffusion coefficient measured by brain diffusion tensor imaging (DTI)
Time frame: end of treatment, an average of 1 per year
Population: Analyses were not completed and will never be completed due to insufficient funding
Secondary
FA
Fractional anisotropy as measured by brain diffusion tensor imaging (DTI)
Time frame: end of treatment, an average of 1 per year
Population: Analyses were not completed and will never be completed due to insufficient funding
Secondary
MRS Lipids
Brain magnetic resonance spectroscopy
Time frame: end of treatment, an average of 1 per year
Population: Analyses were not completed and will never be completed due to insufficient funding
Secondary
MVA
urinary mevalonate excretion
Time frame: through study completion, an average of 2 per year
Population: Analyses were not completed and will never be completed due to insufficient funding
Secondary
Plasma Marker of Sterol Metabolism
Blood cholesterol to 7-dehydrocholesterol ratio
Time frame: through study completion, an average of 2 per year
Population: Analyses were not completed and will never be completed due to insufficient funding
Secondary
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
Time frame: end of treatment, an average of 1 per year
Population: Analyses were not completed and will never be completed due to insufficient funding