Smith-Lemli-Opitz Syndrome
Conditions
Keywords
cholesterol, Smith-Lemli-Opitz syndrome, mental retardation, sterols, congenital anomalies
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.
Interventions
DRUGcrystalline 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.
Sponsors
Boston Children's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Responders | Every 3-6 months for an approximate median of 5 years | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Growth Responders | Every 3-6 months for an approximate median of 5 years | Growth response was defined as an increase in general health, growth, and behavior. |
| Number of Participants With Improved Neuropsychological Development | Every 3-6 months for an approximate median of 5 years | Improved neuropsychological development is defined as progressively achieving developmental milestones |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Cholesterol Supplementation |
|---|---|
| Age, Categorical <=18 years | 18 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 23 |
| serious Total, serious adverse events | 0 / 23 |
Outcome results
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.
Time frame: Every 3-6 months for an approximate median of 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cholesterol Supplementation | Number of Responders | 18 Participants |
Secondary
Number of Growth Responders
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cholesterol Supplementation | Number of Growth Responders | 18 Participants |
Secondary
Number of Participants With Improved Neuropsychological Development
Improved neuropsychological development is defined as progressively achieving developmental milestones
Time frame: Every 3-6 months for an approximate median of 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cholesterol Supplementation | Number of Participants With Improved Neuropsychological Development | 18 Participants |