Short-term Behavioral Effects of Cholesterol Therapy in Smith-Lemli-Opitz Syndrome
This 10-week study will evaluate and compare behavior changes in children with Smith-Lemli-Opitz syndrome (SLOS) who are taking cholesterol supplementation versus those who are not on cholesterol supplementation. SLOS is a genetic disorder that affects the development of children both before and after birth. An enzyme deficiency in these children results in low levels of cholesterol, which can cause a variety of birth defects and behavioral problems. Typical abnormal physical features of patients include a small head, drooping eyelids, small upturned nose, small chin, cleft palate, heart defects, and extra fingers or toes.
Children between 5 and 17 with mild SLOS who do not have a history of egg allergy or intolerance may be eligible for this study. Candidates are screened with a questionnaire about the patient's age, genotype (if known), sterol levels, symptoms, current treatment and medical history.
Children participate in five 2-week study phases. In phases 1, 3 and 5, all children take 150 mg/kg daily of a cholesterol preparation typically used to supplement cholesterol in patients in SLOS studies at NIH. In phases 2 and 4, the participants are randomly assigned to take either egg yolk or an egg yolk substitute, such as Egg Beaters, that does not contain cholesterol. The study is done at the participant's home, and the cholesterol supplementation and egg/egg substitute are sent to the home each day with instructions on how to take them.
The caretakers can stop the blinded phase after four days if behavior problems occur.
The children's caretakers fill out a standard behavioral questionnaire, the Aberrant Behavior Checklist, at the start of the study and after each of the five phases. The questionnaire is designed to assess the effects of treatment in mentally impaired persons.
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Short-Term Behavioral Effects of Cholesterol Therapy in Smith-Lemli-Opitz Syndrome|
- Hyperactivity subscale of the Abberrant Behavior Checklist (ABC). [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
- ABC subscales - inappropriate speech, lethargy, stereotypy, and irritability; Time of caretake tolerance. [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||June 2005|
|Study Completion Date:||February 2009|
|Primary Completion Date:||February 2009 (Final data collection date for primary outcome measure)|
Drug: Cholesterol Suspension
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:
- To quantitatively evaluate behavior, in a blinded study, of SLOS children on and off dietary cholesterol supplementation.
- To quantitatively evaluate behavior in SLOS children treated with egg yolk compared to synthetic dietary cholesterol supplementation.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|