Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00114634
Other study ID # 050168
Secondary ID 05-CH-0168
Status Completed
Phase Phase 2
First received June 15, 2005
Last updated December 24, 2015
Start date June 2005
Est. completion date February 2009

Study information

Verified date December 2015
Source National Institutes of Health Clinical Center (CC)
Contact n/a
Is FDA regulated No
Health authority United States: Federal Government
Study type Interventional

Clinical Trial Summary

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 two 2-week study phases. Between the study phases the children will take 150 mg/kg daily of a cholesterol preparation typically used to supplement cholesterol in patients in SLOS studies at NIH. In the study phases, 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 study phases after four days if behavior problems occur.

The children's caretakers fill out a standard behavioral questionnaire, the Aberrant Behavior Checklist. The questionnaire is designed to assess the effects of treatment in mentally impaired persons.


Description:

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.

Completed study has been published. Tierney, E., Conley, S.K., Goodwin, H., Porter, F.D. (2010) Analysis of short-term behavioral effects of dietary cholesterol supplementation in Smith-Lemli-Opitz Syndrome. Am. J. Med. Genet. Part A. 152A: 91-95 PMID: 20014133


Recruitment information / eligibility

Status Completed
Enrollment 13
Est. completion date February 2009
Est. primary completion date February 2009
Accepts healthy volunteers No
Gender Both
Age group 4 Years to 17 Years
Eligibility Inclusion

1. This study will include pediatric patients, ages 4-17 years old with a biochemical diagnosis of Smith-Lemli-Opitz Syndrome (SLOS).

2. Only mild and classical patients will be enrolled.

3. This study will be open to include SLOS patients regardless of whether or not they are participating in another NIH protocol.

Exclusion

1. Patients with a history of egg allergy or intolerance will be excluded from this study.

2. Subjects must be well enough to be in a home setting.

3. Patients participating in our simvastatin protocol (03-CH-3225) will be excluded from this study.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment


Intervention

Dietary Supplement:
Egg yolk preparation with cholesterol
Egg yolk preparation with cholesterol
Egg substitute, without cholesterol
Placebo control. Egg substitute, without cholesterol

Locations

Country Name City State
United States National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda Maryland

Sponsors (1)

Lead Sponsor Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

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. — View Citation

Kelley RI. A new face for an old syndrome. Am J Med Genet. 1997 Jan 31;68(3):251-6. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Hyperactivity Sub-scale of the Aberrant Behavior Checklist-Community (ABC-C). The Aberrant Behavior Checklist-Community (ABC-C) is a measure used to identify treatment efficacy among intellectually impaired individuals. ABC Subscale IV (Hyperactivity) has 16 items, each can be rated from 0 to 3, with 0 equal to not at all a problems, one the problem is the behavior but slight in degree, to the problem is moderately serious, 3 the problem is severe in degree. For this subscale, score can go from 0 - 48. The higher the score, the worse the hyperactivity. The comparison in this study was made between the blinded phases when patients received either egg yolk (treated, +cholesterol) or egg substitute (untreated, -cholesterol). Order was randomized. 2 weeks No
Secondary ABC Irritability Sub-scale ABC Subscale I (Irritability) has 15 items, each can be rated from 0 to 3, with 0 equal to not at all a problem, 1 the problem is the behavior but slight in degree, 2 the problem is moderately serious, 3 the problem is severe in degree. For this subscale, score can go from 0 - 45 2 weeks No
Secondary ABC Lethargy Sub-scale ABC Subscale II (Lethargy) has 16 items, each can be rated from 0 to 3, with 0 equal to not at all a problems, 1 the problem is the behavior but slight in degree,2 the problem is moderately serious, 3 the problem is severe in degree. For this subscale, score can go from 0 - 48. 2 weeks No
Secondary ABC Stereotypy Sub-scale ABC Subscale III (Stereotypy) has 7 items, each can be rated from 0 to 3, with 0 equal to not at all a problems, 1 the problem is the behavior but slight in degree, 2 the problem is moderately serious, 3 the problem is severe in degree. For this subscale, score can go from 0 - 21. 2 weeks No
Secondary ABC Inappropriate Behavior Sub-scale ABC Subscale V (Inappropriate speech) has 4 items, each can be rated from 0 to 3, with 0 equal to not at all a problems, 1 the problem is the behavior but slight in degree, 2 the problem is moderately serious, 3 the problem is severe in degree. For this subscale, score can go from 0 - 12. 2 weeks No
Secondary ABC Total Score ABC total score includes all the questions from subscales, with range of 0 to 174. Higher the score , the greater the problem. 2 weeks No
See also
  Status Clinical Trial Phase
Terminated NCT01434745 - SLOS: The Effect of Simvastatin in Patients Receiving Cholesterol Supplementation N/A
Completed NCT00001721 - Study of Smith-Lemli-Opitz Syndrome
Recruiting NCT05687474 - Baby Detect : Genomic Newborn Screening
Enrolling by invitation NCT03655223 - Early Check: Expanded Screening in Newborns
Recruiting NCT00004347 - Phase II Study of Dietary Cholesterol for Smith-Lemli-Opitz Syndrome Phase 2
Completed NCT03720990 - Smith-Lemli-Opitz Syndrome and Cholic Acid Phase 1/Phase 2
Completed NCT00017732 - Estimation of the Carrier Frequency and Incidence of Smith-Lemli-Opitz Syndrome in African Americans N/A
Completed NCT00064792 - Simvastatin Therapy in Smith-Lemli-Opitz Syndrome Phase 2
Recruiting NCT05642221 - Functional Near-Infrared Spectroscopy (fNIRS) Combined With Diffuse Correlation Spectroscopy (DCS) in Neurocognitive Disease as Compared to Healthy Neurotypical Controls
Terminated NCT01356420 - Sterol and Isoprenoid Disease Research Consortium: Smith-Lemli-Opitz Syndrome N/A
Completed NCT00272844 - Treatment of the Cholesterol Defect in Smith-Lemli-Opitz Syndrome Phase 1/Phase 2
Recruiting NCT01773278 - Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS) Phase 2
Completed NCT00070850 - Prenatal Screening For Smith-Lemli-Opitz Syndrome Phase 2