Short-term Behavioral Effects of Cholesterol Therapy in Smith-Lemli-Opitz Syndrome

NCT00114634 | Completed Phase 2 Results

• 2 other identifiers: 05016805-CH-0168
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Smith-Lemli-Opitz Syndrome

Keywords

SLOS; RSH syndrome; ABC Checklist; Cholesterol supplementation; Egg yolk; Smith-Lemli-Opitz Syndrome

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• ABC Irritability Sub-scale

  2 weeks

• ABC Lethargy Sub-scale

  2 weeks

• ABC Stereotypy Sub-scale

  2 weeks

• ABC Inappropriate Behavior Sub-scale

  2 weeks

• ABC Total Score

  2 weeks

Study Arms (2)

Egg yolk preparation with cholesterol

EXPERIMENTAL

Dietary cholesterol in the form of liquid egg yolk

Dietary Supplement: Egg yolk preparation with cholesterol

Egg yolk preparation without cholesterol

PLACEBO COMPARATOR

No dietary cholesterol supplementation (egg substitute) Papetti Foods "Better 'n Eggs" egg substitute

Dietary Supplement: Egg substitute, without cholesterol

Interventions

Egg yolk preparation with cholesterol DIETARY_SUPPLEMENT

Egg yolk preparation with cholesterol

Egg yolk preparation with cholesterol

Egg substitute, without cholesterol DIETARY_SUPPLEMENT

Placebo control. Egg substitute, without cholesterol

Egg yolk preparation without cholesterol

Eligibility Criteria

• Age: 4 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• This study will include pediatric patients, ages 4-17 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related 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. doi: 10.1002/(sici)1096-8628(19970131)68:33.0.co;2-x.

  PMID: 9024564 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.

  PMID: 9024565 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.

  PMID: 9024554 BACKGROUND

MeSH Terms

Conditions

Smith-Lemli-Opitz Syndrome

Interventions

Cholesterol

Condition Hierarchy (Ancestors)

Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Membrane Lipids; Lipids

Limitations and Caveats

Poor power due to low enrollment

Results Point of Contact

• Title: Forbes D Porter
• Organization: NICHD, NIH

fdporter@mail.nih.gov

301-435-4432

Study Officials

• Forbes D Porter, MD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Investigator

Study Record Dates

• First Submitted: June 15, 2005
• First Posted: June 16, 2005
• Study Start: June 1, 2005
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: January 29, 2016
• Results First Posted: April 9, 2014

Record last verified: 2015-12

Locations

US (1)