SLOS: The Effect of Simvastatin in Patients Receiving Cholesterol Supplementation

• Sponsor: Oregon Health and Science University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01434745
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 1
• Location: 1
• Arms: 2
• Duration (Months): 37
• Patients Per Site Per Month: 0

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Smith-Lemli-Opitz Syndrome	Drug: Simvastatin; Dietary Supplement: Lactose	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Smith-Lemli Opitz Syndrome: A Clinical Investigation of the Effect of Simvastatin in Patients Receiving Cholesterol Supplementation
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Development Quotient (DQ) [through study completion, an average of 2 per year]

   neurocognitive assessment measured with Mullen Scales of Learning

Secondary Outcome Measures

1. 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

2. Plasma Marker of Sterol Metabolism [through study completion, an average of 2 per year]

   Blood cholesterol to 7-dehydrocholesterol ratio

3. ADC [end of treatment, an average of 1 per year]

   Apparent diffusion coefficient measured by brain diffusion tensor imaging (DTI)

4. MVA [through study completion, an average of 2 per year]

   urinary mevalonate excretion

5. MRS Lipids [end of treatment, an average of 1 per year]

   Brain magnetic resonance spectroscopy

6. FA [end of treatment, an average of 1 per year]

   Fractional anisotropy as measured by brain diffusion tensor imaging (DTI)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 89 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oregon Health and Science University	Portland	Oregon	United States	97239

Sponsors and Collaborators

• Oregon Health and Science University
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Jean-Baptiste Roullet, PhD, Washington State University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jean-Baptiste Roullet, Clinical Professor, Oregon Health and Science University
• ClinicalTrials.gov Identifier: NCT01434745
• Other Study ID Numbers: R01HL073980; R01HL073980
• First Posted: Sep 15, 2011
• Last Update Posted: Oct 1, 2019
• Last Verified: Sep 1, 2019

• Keywords provided by Jean-Baptiste Roullet, Clinical Professor, Oregon Health and Science University: SLOS; Cholesterol Supplementation; Simvastatin
• Additional relevant MeSH terms: Smith-Lemli-Opitz Syndrome; Syndrome; Simvastatin

Study Results

Participant Flow

Recruitment Details	Only one participant enrolled

Arm/Group Title	Placebo - Lactose	Simvastatin
Arm/Group Description	Placebo-Lactose Lactose: Lactose will be administered in a capsule formula.	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
Period Title: Overall Study
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo - Lactose	Simvastatin	Total
Arm/Group Description	Placebo-Lactose Lactose: Lactose will be administered in a capsule formula.	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	Total of all reporting groups
Overall Participants	0	0	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Age () []
Sex: Female, Male () []
Female
Male
Ethnicity (NIH/OMB) () []
Hispanic or Latino
Not Hispanic or Latino
Unknown or Not Reported
Race (NIH/OMB) () []
American Indian or Alaska Native
Asian
Native Hawaiian or Other Pacific Islander
Black or African American
White
More than one race
Unknown or Not Reported
Region of Enrollment (participants) []

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

No funding

Arm/Group Title	Placebo - Lactose	Simvastatin
Arm/Group Description	Placebo-Lactose Lactose: Lactose will be administered in a capsule formula.	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
Measure Participants	0	0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Lactose	Simvastatin
Arm/Group Description	Placebo-Lactose Lactose: Lactose will be administered in a capsule formula.	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
Measure Participants	0	0

3. Secondary Outcome

Title	Plasma Marker of Sterol Metabolism
Description	Blood cholesterol to 7-dehydrocholesterol ratio
Time Frame	through study completion, an average of 2 per year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Lactose	Simvastatin
Arm/Group Description	Placebo-Lactose Lactose: Lactose will be administered in a capsule formula.	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
Measure Participants	0	0

4. Secondary Outcome

Title	ADC
Description	Apparent diffusion coefficient measured by brain diffusion tensor imaging (DTI)
Time Frame	end of treatment, an average of 1 per year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Lactose	Simvastatin
Arm/Group Description	Placebo-Lactose Lactose: Lactose will be administered in a capsule formula.	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
Measure Participants	0	0

5. Secondary Outcome

Title	MVA
Description	urinary mevalonate excretion
Time Frame	through study completion, an average of 2 per year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Lactose	Simvastatin
Arm/Group Description	Placebo-Lactose Lactose: Lactose will be administered in a capsule formula.	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
Measure Participants	0	0

6. Secondary Outcome

Title	MRS Lipids
Description	Brain magnetic resonance spectroscopy
Time Frame	end of treatment, an average of 1 per year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Lactose	Simvastatin
Arm/Group Description	Placebo-Lactose Lactose: Lactose will be administered in a capsule formula.	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
Measure Participants	0	0

7. Secondary Outcome

Title	FA
Description	Fractional anisotropy as measured by brain diffusion tensor imaging (DTI)
Time Frame	end of treatment, an average of 1 per year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Lactose	Simvastatin
Arm/Group Description	Placebo-Lactose Lactose: Lactose will be administered in a capsule formula.	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
Measure Participants	0	0

Adverse Events

Time Frame	3 years
Arm/Group Title	Placebo - Lactose		Simvastatin
Arm/Group Description	Placebo-Lactose Lactose: Lactose will be administered in a capsule formula.		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
All Cause Mortality
	Placebo - Lactose		Simvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo - Lactose		Simvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Placebo - Lactose		Simvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)

Limitations/Caveats

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

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.