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| ID | Type | Description | Link |
|---|---|---|---|
| 05-CH-0168 | Other Identifier | NIH CC |
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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.
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:
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Egg yolk preparation with cholesterol | Experimental | Dietary cholesterol in the form of liquid egg yolk |
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| Egg yolk preparation without cholesterol | Placebo Comparator | No dietary cholesterol supplementation (egg substitute) Papetti Foods "Better 'n Eggs" egg substitute |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Egg yolk preparation with cholesterol | Dietary Supplement | Egg yolk preparation with cholesterol |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion
Exclusion
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| Name | Affiliation | Role |
|---|---|---|
| Forbes D Porter, MD | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9024564 | Background | 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. doi: 10.1002/(sici)1096-8628(19970131)68:33.0.co;2-x. | |
| 9024565 | Background | 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. |
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no exclusions
October to July 2008
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| ID | Title | Description |
|---|---|---|
| FG000 | Egg Yolk or no Egg Yolk | This was a double-blind, placebo-controlled, cross-over design. The trial was composed of five 2-week phases. Two phases, phases 2 and 4, were double-blinded. During these phases, subjects were either on placebo (egg substitute with no cholesterol) or cholesterol supplementation (pasteurized egg yolk). During the interval phases, 1, 3 and 5, subjects were maintained on baseline therapy of 150 mg/kg/day of crystalline cholesterol suspended in Ora-Plus. Order of placebo versus cholesterol was random with 6 subjects receiving placebo first (in phase 2) and 4 subjects receiving cholesterol containing pasteurized egg yolk first. 13 subjects were enrolled, only 10 subjects completed the study. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Egg substitute, without cholesterol | Dietary Supplement | Placebo control. Egg substitute, without cholesterol |
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| 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 |
| 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 |
| 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 |
| 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 |
| 9024554 | Background | Kelley RI. A new face for an old syndrome. Am J Med Genet. 1997 Jan 31;68(3):251-6. doi: 10.1002/(sici)1096-8628(19970131)68:33.0.co;2-p. No abstract available. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Egg Yolk or no Egg Yolk | All subjects were on cholesterol suspension or egg yolk versus no egg yolk. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
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| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Severity score | Severity score ranges from 0-100; the higher the score the greater the severity | Median | Full Range | units on a scale |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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. | Posted | Mean | Standard Error | units on a scale | 2 weeks |
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| 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 | Posted | Mean | Standard Error | units on a scale | 2 weeks |
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| 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. | Posted | Mean | Standard Error | units on a scale | 2 weeks |
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| 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. | Posted | Mean | Standard Error | units on a scale | 2 weeks |
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| 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. | Posted | Mean | Standard Error | units on a scale | 2 weeks |
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| 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. | Posted | Mean | Standard Error | units on a scale | 2 weeks |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group 1 | All subjects were on cholesterol suspension or egg yolk versus no egg yolk. | 0 | 13 | 0 | 13 |
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Poor power due to low enrollment
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Forbes D Porter | NICHD, NIH | 301-435-4432 | fdporter@mail.nih.gov |
| ID | Term |
|---|---|
| D019082 | Smith-Lemli-Opitz Syndrome |
| ID | Term |
|---|---|
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008052 | Lipid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D043202 | Steroid Metabolism, Inborn Errors |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D002784 | Cholesterol |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013261 | Sterols |
| D008563 | Membrane Lipids |
| D008055 | Lipids |
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