Treatment of the Cholesterol Defect in Smith-Lemli-Opitz Syndrome

Smith-Lemli-Opitz Syndrome Clinical Trial

Official title:

Treatment of the Cholesterol Defect in Smith-Lemli-Opitz Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00272844
• Other study ID #: 03-11-189R
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 4, 2006
• Last updated: September 21, 2017
• Start date: January 1998
• Est. completion date: July 2011

Study information

• Verified date: September 2017
• Source: Boston Children’s Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: July 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Cleft Palate
• Genetic Diseases, X-Linked
• Hypospadias
• Smith-Lemli-Opitz Syndrome
• Syndrome

Intervention

Drug:
• crystalline cholesterol oil-based suspension
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.

Locations

Country	Name	City	State
United States	Children's Hospital Boston	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Boston Children’s Hospital

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — 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

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( — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Responders	Responders was defined as an increase in total serum cholesterol and a decrease in 7-DHC (7-Dehydrocholesterol), and 8-DHC (8-Dehydrocholesterol) were measured on all participants.	Every 3-6 months for an approximate median of 5 years
Secondary	Number of Growth Responders	Growth response was defined as an increase in general health, growth, and behavior.	Every 3-6 months for an approximate median of 5 years
Secondary	Number of Participants With Improved Neuropsychological Development	Improved neuropsychological development is defined as progressively achieving developmental milestones	Every 3-6 months for an approximate median of 5 years