Clinical Trial: Short-Term Behavioral Effects of Cholesterol Therapy in Smith-Lemli-Opitz Syndrome

This study is currently recruiting patients.

Sponsored by: National Institute of Child Health and Human Development (NICHD)
Information provided by: Warren G Magnuson Clinical Center (CC)

Purpose

Smith-Lemli- Opitz syndrome (SLOS) is an autosomal recessive genetic condition caused by a deficiency of the enzyme 3beta-hydroxysterol delta(7)- reductase (DHCR7). DHCR7 is the final enzyme in the sterol synthetic pathway and converts 7- dehydrocholesterol (7DHC) to cholesterol. This results in low cholesterol and elevated 7DHC levels. SLOS has a wide phenotypic spectrum. Mildly affected individuals may have subtle dysmorphic features along with learning and behavioral disabilities. Typical clinical manifestations include microcephaly, ptosis, anteversion of the nostrils, micrognathia, high arched or cleft palate, congenital heart defects, clinodactyly, post- axial polydactyly, and 2-3 toe syndactyly. More severely affected individuals have multiple congenital anomalies, may be miscarried, stillborn, or die within the first few weeks of life.
Dietary cholesterol supplementation in children with SLOS is reported to improve behavior, growth and nutritional status. Based upon observational studies, the behavioral changes reported with dietary cholesterol supplementation occur rapidly and appear to be reversible. Parental reports of improved behavior could be influenced by a placebo effect. Thus, we are proposing a blinded study to compare behavioral changes while the patient is on cholesterol supplementation (egg yolk) versus no cholesterol supplementation (egg substitute).
The objectives of this study are:
1. To quantitatively evaluate behavior, in a blinded study, of SLOS children on and off dietary cholesterol supplementation.
2. To quantitatively evaluate behavior in SLOS children treated with egg yolk compared to synthetic dietary cholesterol supplementation.
Intervention Phase
 Drug: Cholesterol Suspension
Phase II

MedlinePlus consumer health information 

Study Type: Interventional
Study Design: Treatment, Safety/Efficacy

Further Study Details: 

Expected Total Enrollment:  40

Study start: June 13, 2005

Smith-Lemli- Opitz syndrome (SLOS) is an autosomal recessive genetic condition caused by a deficiency of the enzyme 3beta-hydroxysterol delta(7)- reductase (DHCR7). DHCR7 is the final enzyme in the sterol synthetic pathway and converts 7- dehydrocholesterol (7DHC) to cholesterol. This results in low cholesterol and elevated 7DHC levels. SLOS has a wide phenotypic spectrum. Mildly affected individuals may have subtle dysmorphic features along with learning and behavioral disabilities. Typical clinical manifestations include microcephaly, ptosis, anteversion of the nostrils, micrognathia, high arched or cleft palate, congenital heart defects, clinodactyly, post- axial polydactyly, and 2-3 toe syndactyly. More severely affected individuals have multiple congenital anomalies, may be miscarried, stillborn, or die within the first few weeks of life.
Dietary cholesterol supplementation in children with SLOS is reported to improve behavior, growth and nutritional status. Based upon observational studies, the behavioral changes reported with dietary cholesterol supplementation occur rapidly and appear to be reversible. Parental reports of improved behavior could be influenced by a placebo effect. Thus, we are proposing a blinded study to compare behavioral changes while the patient is on cholesterol supplementation (egg yolk) versus no cholesterol supplementation (egg substitute).
The objectives of this study are:
1. To quantitatively evaluate behavior, in a blinded study, of SLOS children on and off dietary cholesterol supplementation.
2. To quantitatively evaluate behavior in SLOS children treated with egg yolk compared to synthetic dietary cholesterol supplementation.

Eligibility

Genders Eligible for Study:  Both
Criteria
INCLUSION CRITERIA:
This study will include pediatric patients, ages 5-17 years old with a biochemical diagnosis of Smith-Lemli-Opitz Syndrome (SLOS). Only mild and classical patients will be enrolled. This study will be open to include SLOS patients regardless of whether or not they are participating in another NIH protocol.
EXCLUSION CRITERIA:
Patients with a history of egg allergy or intolerance will be excluded from this study. Subjects must be well enough to be in a home setting. Patients participating in our simvastatin protocol (03-CH-3225) will be excluded from this study.

Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier  NCT00114634


Maryland
      National Institute of Child Health and Human Development (NICHD), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Patient Recruitment and Public Liaison Office  1-800-411-1222    prpl@mail.cc.nih.gov 
TTY  1-866-411-1010 

More Information

Detailed Web Page

Publications

Elias ER, Irons MB, Hurley AD, Tint GS, Salen G. Clinical effects of cholesterol supplementation in six patients with the Smith-Lemli-Opitz syndrome (SLOS) Am J Med Genet. 1997 Jan 31;68(3):305-10.

Irons M, Elias ER, Abuelo D, Bull MJ, Greene CL, Johnson VP, Keppen L, Schanen C, Tint GS, Salen G. Treatment of Smith-Lemli-Opitz syndrome: results of a multicenter trial. Am J Med Genet. 1997 Jan 31;68(3):311-4.

Kelley RI. A new face for an old syndrome. Am J Med Genet. 1997 Jan 31;68(3):251-6. No abstract available.

Study ID Numbers:  050168; 05-CH-0168
Record last reviewed:  June 6, 2005
Last Updated:  June 23, 2005
Record first received:  June 15, 2005
ClinicalTrials.gov Identifier:  NCT00114634
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-07-05

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