Clinical trial NCT00272844: Treatment of the Cholesterol Defect in Smith-Lemli-Opitz Syndrome
Official title: Treatment of the Cholesterol Defect in Smith-Lemli-Opitz Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Smith-Lemli-Opitz Syndrome
Keywords: cholesterol
Smith-Lemli-Opitz syndrome
mental retardation
sterols
congenital anomalies
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
First posted: 2006-01-09
Enrollment: 23
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Number of Responders
timeFrame: Every 3-6 months for an approximate median of 5 years
Secondary outcomes:
measure: Number of Growth Responders
timeFrame: Every 3-6 months for an approximate median of 5 years
measure: Number of Participants With Improved Neuropsychological Development
timeFrame: Every 3-6 months for an approximate median of 5 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Mira Irons, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1002/ajmg.1320500409.
citation: 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.
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.
citation: 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. doi: 10.1007/s00234-003-1110-1. Epub 2003 Nov 5.
citation: 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. doi: 10.1001/archopht.121.12.1738.