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

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.

Study Overview

• Status: Completed
• Conditions: Smith-Lemli-Opitz Syndrome
• Intervention / Treatment: Drug: crystalline cholesterol oil-based suspension

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cholesterol supplementation	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Investigators: Principal Investigator: Mira Irons, M.D., Boston Children's Hospital

Publications and helpful links

General 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. doi: 10.1002/ajmg.1320500409.
• 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.
• 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. doi: 10.1007/s00234-003-1110-1. 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. doi: 10.1001/archopht.121.12.1738.

Study record dates

Study Major Dates

• Study Start: January 1, 1998
• Primary Completion (ACTUAL): June 1, 2011
• Study Completion (ACTUAL): July 1, 2011

Study Registration Dates

• First Submitted: January 4, 2006
• First Submitted That Met QC Criteria: January 4, 2006
• First Posted (ESTIMATE): January 9, 2006

Study Record Updates

• Last Update Posted (ACTUAL): October 20, 2017
• Last Update Submitted That Met QC Criteria: September 21, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: cholesterol; mental retardation; Smith-Lemli-Opitz syndrome; sterols; congenital anomalies
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Stomatognathic Diseases; Mouth Diseases; Bone Diseases; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Dyslipidemias; Mouth Abnormalities; Stomatognathic System Abnormalities; Jaw Abnormalities; Jaw Diseases; Maxillofacial Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Abnormalities, Multiple; Lipid Metabolism, Inborn Errors; Bone Diseases, Developmental; Steroid Metabolism, Inborn Errors; Penile Diseases; Craniofacial Dysostosis; Dysostoses; Syndrome; Cleft Palate; Hypospadias; Genetic Diseases, X-Linked; Smith-Lemli-Opitz Syndrome; Hypertelorism
• Other Study ID Numbers: 03-11-189R