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

Primary Purpose

Smith-Lemli-Opitz Syndrome

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
crystalline cholesterol oil-based suspension
Sponsored by
Boston Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Smith-Lemli-Opitz Syndrome focused on measuring cholesterol, Smith-Lemli-Opitz syndrome, mental retardation, sterols, congenital anomalies

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital Boston

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cholesterol supplementation

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Number of Growth Responders
Growth response was defined as an increase in general health, growth, and behavior.
Number of Participants With Improved Neuropsychological Development
Improved neuropsychological development is defined as progressively achieving developmental milestones

Full Information

First Posted
January 4, 2006
Last Updated
September 21, 2017
Sponsor
Boston Children's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT00272844
Brief Title
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

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
January 1998 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
July 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Boston Children's Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Smith-Lemli-Opitz Syndrome
Keywords
cholesterol, Smith-Lemli-Opitz syndrome, mental retardation, sterols, congenital anomalies

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cholesterol supplementation
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
crystalline cholesterol oil-based suspension
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Responders
Description
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.
Time Frame
Every 3-6 months for an approximate median of 5 years
Secondary Outcome Measure Information:
Title
Number of Growth Responders
Description
Growth response was defined as an increase in general health, growth, and behavior.
Time Frame
Every 3-6 months for an approximate median of 5 years
Title
Number of Participants With Improved Neuropsychological Development
Description
Improved neuropsychological development is defined as progressively achieving developmental milestones
Time Frame
Every 3-6 months for an approximate median of 5 years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mira Irons, M.D.
Organizational Affiliation
Boston Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8209913
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.
Results Reference
result
PubMed Identifier
9024564
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.
Results Reference
result
PubMed Identifier
9024565
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.
Results Reference
result
PubMed Identifier
14605787
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.
Results Reference
result
PubMed Identifier
14662594
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.
Results Reference
result

Learn more about this trial

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

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