Treatment of the Cholesterol Defect in Smith-Lemli-Opitz Syndrome - Full Text View

Purpose

The purpose of this study is to determine whether supplementation with an oil-based cholesterol suspension will correct the biochemical abnormalities in cholesterol and its precursors in individuals with the Smith-Lemli-Opitz syndrome.

Condition	Intervention	Phase
Smith-Lemli-Opitz Syndrome	Drug: crystalline cholesterol oil-based suspension	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Treatment of the Cholesterol Defect in Smith-Lemli-Opitz Syndrome

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease Farber lipogranulomatosis Smith-Lemli-Opitz syndrome

MedlinePlus related topics: Cholesterol

U.S. FDA Resources

Further study details as provided by Children's Hospital Boston:

Primary Outcome Measures:

Improvement in sterol levels monitored q.3-6 months [ Time Frame: q. 3-6 months over 20+ years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Improved general health, growth, and behavior [ Time Frame: q. 3-6 months over 20 years ] [ Designated as safety issue: Yes ]
Improved neuropsychological development [ Time Frame: q. 3-6 months over 20+ years ] [ Designated as safety issue: No ]

Enrollment:	23
Study Start Date:	January 1998
Study Completion Date:	July 2011
Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Intervention Details:

200 mg/mL suspension of crystalline cholesterol in oil. Dosage (generally 75-300 mg/kg/day in divided doses) is based on initial cholesterol levels and regulated to increase, yet maintain, cholesterol levels no higher than normal ranges.

Detailed Description:

This study involves treating individuals with the Smith-Lemli-Opitz syndrome, a rare inborn error of cholesterol metabolism, with supplemental cholesterol to determine it effects on biochemical sterol metabolites, growth, neuropsychological development, ophthalmologic and auditory function, ERG (electroretinogram) parameters, and CNS metabolites as determined by brain MRS-imaging. Safety of the supplemental cholesterol suspension is monitored by tests of hematologic, renal, and liver function at periodic intervals. There is also a substudy that is investigating potential genotype-phenotype correlations, as well as another that studies biochemical parameters of light sensitivity in cultured skin fibroblasts from affected patients.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Biochemical confirmation of sterol defect associated with Smith-Lemli-Opitz syndrome

Exclusion Criteria:

Inability to tolerate crystalline cholesterol
Inability to travel to Boston 3-4 times/year based on age

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00272844

Locations

United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Children's Hospital Boston

Investigators

Principal Investigator:

Mira Irons, M.D.

Children's Hospital Boston

More Information

Publications:

Irons M, Elias ER, Tint GS, Salen G, Frieden R, Buie TM, Ampola M. Abnormal cholesterol metabolism in the Smith-Lemli-Opitz syndrome: report of clinical and biochemical findings in four patients and treatment in one patient. Am J Med Genet. 1994 May 1;50(4):347-52.

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.

Caruso PA, Poussaint TY, Tzika AA, Zurakowski D, Astrakas LG, Elias ER, Bay C, Irons MB. MRI and 1H MRS findings in Smith-Lemli-Opitz syndrome. Neuroradiology. 2004 Jan;46(1):3-14. Epub 2003 Nov 5.

Elias ER, Hansen RM, Irons M, Quinn NB, Fulton AB. Rod photoreceptor responses in children with Smith-Lemli-Opitz syndrome. Arch Ophthalmol. 2003 Dec;121(12):1738-43.

Responsible Party:	Mira Irons M.D., Children's Hospital Boston
ClinicalTrials.gov Identifier:	NCT00272844 History of Changes
Other Study ID Numbers:	03-11-189R
Study First Received:	January 4, 2006
Last Updated:	July 13, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Children's Hospital Boston:

cholesterol
Smith-Lemli-Opitz syndrome
mental retardation
sterols
congenital anomalies

Additional relevant MeSH terms:

Smith-Lemli-Opitz Syndrome
Abnormalities, Multiple
Congenital Abnormalities
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors

Genetic Diseases, Inborn
Steroid Metabolism, Inborn Errors
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on June 18, 2013