Cholesterol in ASD: Characterization and Treatment
|ClinicalTrials.gov Identifier: NCT00965068|
Recruitment Status : Completed
First Posted : August 25, 2009
Last Update Posted : October 6, 2017
|First Submitted Date ICMJE||August 24, 2009|
|First Posted Date ICMJE||August 25, 2009|
|Last Update Posted Date||October 6, 2017|
|Study Start Date ICMJE||July 28, 2009|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00965068 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Cholesterol in ASD: Characterization and Treatment|
|Official Title ICMJE||Cholesterol in Autism Spectrum Disorder (ASD): Characterization and Treatment|
- 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.
- Children between the ages of 4 and 12 who have been diagnosed with an autism spectrum disorder.
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.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Intervention ICMJE||Other: Cholesterol|
|Study Arms||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Enrollment ICMJE
|Actual Study Completion Date||November 14, 2013|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
(No subjects will be excluded based on race, ethnicity or gender).
Double-Blind, Placebo-Controlled trial phase for ASD+Hypo Only:
-Same exclusion criteria as the Characterization Visit.
Open-Label Trial for ASD+Hypo only:
- Subject continues to meet double-blind, placebo-controlled trial phase inclusion criteria.
- Subject started a neuroleptic medication or medication that affects cholesterol synthesis or metabolism.
Family Members of ASD+Hypo only:
- Biological parent(s) and full or half-sibling(s) of any age.
- Those individuals not willing to provide a blood sample or a saliva sample for DNA.
|Ages||4 Years to 12 Years (Child)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00965068|
|Other Study ID Numbers ICMJE||090203
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )|
|Study Sponsor ICMJE||Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||June 8, 2015|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP