Ignite Creation Date:
2025-12-24 @ 5:54 PM
Ignite Modification Date:
2025-12-30 @ 11:26 PM
Study NCT ID:
NCT00965068
Status:
COMPLETED
Last Update Posted:
2018-07-05
First Post:
2009-08-24
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Cholesterol in ASD: Characterization and Treatment
Sponsor:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Organization:
Study Overview
Official Title:
Cholesterol in Autism Spectrum Disorder (ASD): Characterization and Treatment
Status:
COMPLETED
Status Verified Date:
2015-06-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background:
\- Autism spectrum disorders (ASD) are developmental disabilities characterized by impaired social interaction and repetitive and/or stereotypical behaviors. Research studies suggest that some individuals with ASD have very low blood cholesterol levels. This low cholesterol level and other abnormal sterol levels may be important markers for
subtypes of ASD. Providing additional cholesterol to the diets of children with ASD may help improve behavior.
\- These findings will guide the medical community in identifying individuals who should be tested for sterol disorders. This study will also help researchers learn whether adding extra cholesterol to the diet will improve behavioral and other autism spectrum characteristics seen in individuals with ASD and low cholesterol.
Objectives:
* To determine cholesterol levels in children with autism spectrum disorders.
* To compare behavioral and other characteristics among children who have autism spectrum disorders and high, low, or normal cholesterol levels.
* To determine whether adding cholesterol to the diet will improve behavioral and other characteristics in individuals with ASD and low cholesterol.
Eligibility:
\- Children between the ages of 4 and 12 who have been diagnosed with an autism spectrum disorder.
Design:
* Initial screening study will involve a collection of blood samples (for study purposes and cholesterol testing).
* Children who have low cholesterol levels will take part in a study in which they will receive either cholesterol supplementation or a placebo, and will have detailed physical and psychological examinations to measure possible improvement in behavioral or other characteristics.
* Children who have high or normal cholesterol levels will have further blood samples taken, and will undergo an additional set of examinations for comparison purposes.
* Researchers may request blood or DNA samples from other family members (parents or siblings), which will be collected through blood draws and cheek swabs.
\- Autism spectrum disorders (ASD) are developmental disabilities characterized by impaired social interaction and repetitive and/or stereotypical behaviors. Research studies suggest that some individuals with ASD have very low blood cholesterol levels. This low cholesterol level and other abnormal sterol levels may be important markers for
subtypes of ASD. Providing additional cholesterol to the diets of children with ASD may help improve behavior.
\- These findings will guide the medical community in identifying individuals who should be tested for sterol disorders. This study will also help researchers learn whether adding extra cholesterol to the diet will improve behavioral and other autism spectrum characteristics seen in individuals with ASD and low cholesterol.
Objectives:
* To determine cholesterol levels in children with autism spectrum disorders.
* To compare behavioral and other characteristics among children who have autism spectrum disorders and high, low, or normal cholesterol levels.
* To determine whether adding cholesterol to the diet will improve behavioral and other characteristics in individuals with ASD and low cholesterol.
Eligibility:
\- Children between the ages of 4 and 12 who have been diagnosed with an autism spectrum disorder.
Design:
* Initial screening study will involve a collection of blood samples (for study purposes and cholesterol testing).
* Children who have low cholesterol levels will take part in a study in which they will receive either cholesterol supplementation or a placebo, and will have detailed physical and psychological examinations to measure possible improvement in behavioral or other characteristics.
* Children who have high or normal cholesterol levels will have further blood samples taken, and will undergo an additional set of examinations for comparison purposes.
* Researchers may request blood or DNA samples from other family members (parents or siblings), which will be collected through blood draws and cheek swabs.
Detailed Description:
Pilot work suggests that some individuals with autism spectrum disorders (ASD) have very low blood cholesterol levels. This low cholesterol level and other abnormal sterol levels may be important markers for subtypes of ASD. The proposed trial aims to characterize any clinical differences between low-cholesterol ASD and normal-or-high-cholesterol ASD and to test the response of individuals with ASD and low cholesterol to increased cholesterol in the diet.
Evidence for the role of low cholesterol in causing ASD in a subgroup of individuals comes from five sources. First, half of individuals with Smith-Lemli-Opitz syndrome (SLOS) meet the behavioral criteria for autistic disorder (Tierney et al, 2001), and three quarters have some type of ASD (Sikora et al, 2006). Second, in individuals with SLOS, the lower the cholesterol was in the blood and cerebrospinal fluid, the more severe were the autism and IQ and adaptive function deficits. Third, in SLOS, improvement was found in social and communication abilities with added dietary cholesterol. Fourth, cholesterol was low in a pilot study of 100 children with autism of unknown cause (Tierney et al, 2006). Fifth, it is becoming increasingly clear that cholesterol plays a pivotal role in several aspects of brain development.
This proposal is designed to 1) determine the prevalence of hypocholesterolemia in ASD individuals (ASD+Hypo); 2) determine the prevalence of hypercholesterolemia (in ASD individuals (ASD+Hyper); 3) determine the rate of SLOS in the ASD subjects; 4) determine the phenotype (physical, behavioral, and developmental) at less than the 5th centile (ASD+Hypo) and greater than the 95th centile (ASD+Hyper) individuals and normal cholesterol (ASD+Normal) in the ASD subjects; 5) test the efficacy of dietary cholesterol supplementation in ASD individuals with hypocholesterolemia; 6) determine whether a raised dose of cholesterol supplementation is more effective than a lower dose; and 7) create a repository of biomaterial samples from individuals with ASD and their biological family members.
Three sites (Kennedy Krieger Institute \[KKI\], Ohio State University \[OSU\], and the National Institutes of Health \[NIH\]) will collaborate to accomplish the objectives of this study. In addition to defining the frequency of altered cholesterol homeostasis in ASD, 60 youths (20 at each site) with ASD plus hypocholesterolemia will enter a 12-week, double-blind, placebo-controlled trial immediately followed by a 12-week open-label cholesterol trial to test the efficacy of dietary cholesterol supplementation. Outcome measures will include standard tests of behavior, communication, and other autism features.
These findings will guide the medical community in identifying individuals who should be tested for sterol disorders. This study will also help researchers learn whether adding extra cholesterol to the diet will improve behavioral and other autism spectrum characteristics seen in individuals with ASD and low cholesterol. The results of this study may help individuals with hypocholesterolemic ASD by the knowledge of the therapeutic value and safety of the use of cholesterol supplementation both biochemically and behaviorally. If improvement is demonstrated, it opens a new window to understanding the neurologic mechanisms of ASD. This knowledge may also be helpful for hypocholesterolemic individuals with ASD in that this newly identified population will benefit from such supplementation. Even if cholesterol supplementation is found to not be effective, important behavioral phenotype and developmental information will be obtained that might be useful in identifying subjects with ASD plus cholesterol abnormalities.
Evidence for the role of low cholesterol in causing ASD in a subgroup of individuals comes from five sources. First, half of individuals with Smith-Lemli-Opitz syndrome (SLOS) meet the behavioral criteria for autistic disorder (Tierney et al, 2001), and three quarters have some type of ASD (Sikora et al, 2006). Second, in individuals with SLOS, the lower the cholesterol was in the blood and cerebrospinal fluid, the more severe were the autism and IQ and adaptive function deficits. Third, in SLOS, improvement was found in social and communication abilities with added dietary cholesterol. Fourth, cholesterol was low in a pilot study of 100 children with autism of unknown cause (Tierney et al, 2006). Fifth, it is becoming increasingly clear that cholesterol plays a pivotal role in several aspects of brain development.
This proposal is designed to 1) determine the prevalence of hypocholesterolemia in ASD individuals (ASD+Hypo); 2) determine the prevalence of hypercholesterolemia (in ASD individuals (ASD+Hyper); 3) determine the rate of SLOS in the ASD subjects; 4) determine the phenotype (physical, behavioral, and developmental) at less than the 5th centile (ASD+Hypo) and greater than the 95th centile (ASD+Hyper) individuals and normal cholesterol (ASD+Normal) in the ASD subjects; 5) test the efficacy of dietary cholesterol supplementation in ASD individuals with hypocholesterolemia; 6) determine whether a raised dose of cholesterol supplementation is more effective than a lower dose; and 7) create a repository of biomaterial samples from individuals with ASD and their biological family members.
Three sites (Kennedy Krieger Institute \[KKI\], Ohio State University \[OSU\], and the National Institutes of Health \[NIH\]) will collaborate to accomplish the objectives of this study. In addition to defining the frequency of altered cholesterol homeostasis in ASD, 60 youths (20 at each site) with ASD plus hypocholesterolemia will enter a 12-week, double-blind, placebo-controlled trial immediately followed by a 12-week open-label cholesterol trial to test the efficacy of dietary cholesterol supplementation. Outcome measures will include standard tests of behavior, communication, and other autism features.
These findings will guide the medical community in identifying individuals who should be tested for sterol disorders. This study will also help researchers learn whether adding extra cholesterol to the diet will improve behavioral and other autism spectrum characteristics seen in individuals with ASD and low cholesterol. The results of this study may help individuals with hypocholesterolemic ASD by the knowledge of the therapeutic value and safety of the use of cholesterol supplementation both biochemically and behaviorally. If improvement is demonstrated, it opens a new window to understanding the neurologic mechanisms of ASD. This knowledge may also be helpful for hypocholesterolemic individuals with ASD in that this newly identified population will benefit from such supplementation. Even if cholesterol supplementation is found to not be effective, important behavioral phenotype and developmental information will be obtained that might be useful in identifying subjects with ASD plus cholesterol abnormalities.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 09-CH-0203 | None | None | View |