Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cholesterol supplementation | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| crystalline cholesterol oil-based suspension | Drug | 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. |
| 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 |
| 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Mira Irons, M.D. | Boston Children's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Boston | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8209913 | Result | 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. | |
| 9024564 | Result | 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. |
Not provided
Not provided
Not provided
Patients newly diagnosed with Smith-Lemli-Opitz syndrome at Boston Children's Hospital were offered enrollment in the study from 1998 until it's completion. The study was completed and closed to enrollment here in June, 2010 and the IND was withdrawn in July, 2011.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Cholesterol Supplementation | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All patients had elevation of 7-DHC diagnostic of SLOS
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Cholesterol Supplementation | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Count of Participants | Participants | Every 3-6 months for an approximate median of 5 years |
|
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cholesterol Supplementation | 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. |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Mira Irons | Boston Children's Hospital | 617-355-2449 | mira.irons@childrens.harvard.edu |
Not provided
| ID | Term |
|---|---|
| D019082 | Smith-Lemli-Opitz Syndrome |
| D008607 | Intellectual Disability |
| D000013 | Congenital Abnormalities |
| ID | Term |
|---|---|
| D000015 | Abnormalities, Multiple |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008052 | Lipid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
Improved neuropsychological development is defined as progressively achieving developmental milestones
| Every 3-6 months for an approximate median of 5 years |
| 9024565 | Result | 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. |
| 14605787 | Result | 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. |
| 14662594 | Result | 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. |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Participants |
|
|
| Secondary | Number of Growth Responders | Growth response was defined as an increase in general health, growth, and behavior. | Posted | Count of Participants | Participants | 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 | Posted | Count of Participants | Participants | Every 3-6 months for an approximate median of 5 years |
|
|
|
| 0 |
| 23 |
| 0 |
| 23 |
Not provided
Not provided
Not provided
| D030342 | Genetic Diseases, Inborn |
| D043202 | Steroid Metabolism, Inborn Errors |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |