SLOS: The Effect of Simvastatin in Patients Receiving Cholesterol Supplementation

NCT01434745 — Not applicable, Terminated, 1 participants, Oregon Health and Science University

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

Registry	NCT01434745
Status	Terminated - poor enrollment (only one subject enrolled)
Phase	Not applicable
Study type	Interventional; randomized, crossover, masking: single, treatment
Enrollment	1 (Actual)
Sponsor	Oregon Health and Science University (Other); collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Conditions	Smith-Lemli-Opitz Syndrome
Interventions	Simvastatin, Lactose (Drug, dietary supplement)
Dates	start 2011-09-01, primary completion 2014-10-01, completion 2014-10-01, first posted 2011-09-15, last updated 2019-10-01
Locations	1 site in United States

-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.

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+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.

+Arms and interventions

Arm	Type	Interventions	Description
Placebo	Placebo comparator	Dietary Supplement: Lactose	placebo
Simvastatin	Experimental	Drug: Simvastatin	0.5 mg/kg body weight/day

Simvastatin (Drug), also known as Zocor, Flolipid: Simvastatin will be administered as a powder mixed with lactose at the dose of 0.5 mg/kg/day
Lactose (Dietary supplement): Lactose will be administered in a capsule formula.

+Outcome measures

Primary outcomes

Development Quotient (DQ) [through study completion, an average of 2 per year]: neurocognitive assessment measured with Mullen Scales of Learning

Secondary outcomes

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
ADC [end of treatment, an average of 1 per year]: Apparent diffusion coefficient measured by brain diffusion tensor imaging (DTI)
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
FA [end of treatment, an average of 1 per year]: Fractional anisotropy as measured by brain diffusion tensor imaging (DTI)

+Eligibility

Sex: All, ages: 1 Year to 89 Years

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

+Posted results

Participant flow

Milestone	Placebo - Lactose	Simvastatin
Started	0	0
Completed	0	0
Not completed	0	0

Outcome results

Development Quotient (DQ) (Primary)
Whole Body Cholesterol Pool Size, Synthesis & Absorption Using Stable Isotope Testing (Secondary)
Plasma Marker of Sterol Metabolism (Secondary)
ADC (Secondary)
MVA (Secondary)
MRS Lipids (Secondary)
FA (Secondary)

Adverse events

Time frame: 3 years

Arm	Deaths	Serious adverse events	Other adverse events
Placebo - Lactose	0	0/1 (0.0%)	0/1 (0.0%)
Simvastatin	0	0/1 (0.0%)	0/1 (0.0%)

Limitations and caveats: Analyses were not completed and will never be completed due to insufficient funding

+Locations (1)

Facility	City	Country	Status
Oregon Health and Science University	Portland, Oregon	United States

+Investigators

Jean-Baptiste Roullet, PhD, Principal investigator, Washington State University

+Funding

NIH grants: R01HL073980

My Notes

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