AutismPhase 1/2NCT00965068
Cholesterol in ASD: Characterization and Treatment
A Phase 1/2 study testing Cholesterol in people with Autism and Asperger Disorder, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 12 years
- Conditions the study is for
- Autism, Asperger Disorder, PDD-NOS
- What is being tested?
- Cholesterol
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Jul 2009to 14 Nov 2013
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Screening Visit:
- Parents agree to use a multivitamin with minerals if their child is selected to continue to the cholesterol supplementation clinical trial.
- Parents agree to not change the doses of other dietary supplement throughout the clinical trial, including megavitamins.
- Supplements or medications that are not meant to lower cholesterol levels but are likely to have cholesterol-lowering effects (such as Omega 3 or fish oil) will be permitted if the dose has been stable for at least 3 months prior to the initial screening visit.
- Male or female between the ages of 4.0-12.0 years at the time of consent/assent.
- Clinically diagnosed with an ASD for which no cause has been detected.
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- Anticonvulsants used for the treatment of a seizure disorder will be permitted if the dosage has been stable for 3 months, and the subject is seizure free for at least 3 months.
- Same inclusion criteria as the Screening Visit.
- Participants must have a mental age of 18 months as measured at the Characterization Visit by the age-appropriate form of the Stanford Binet-V, the Differential Abilities Scale, or the Mullen Scales of Early Learning (N.B. potential subjects who test below 18 months of age, but are otherwise eligible, may be admitted to the study following a case review convened by the Multisite Steering Committee).
- Child must have an ASD diagnosis using DSM-IV and clinical judgment in order to proceed to the other components of the Characterization Visit.
- Neuroleptics will be permitted for the ASD+Hypo group only if the dosage remains stable for the duration of the study.
- Neuroleptic medication free for at least three months (ASD+Hyper and ASD+Normal only).
- Met Characterization Visit inclusion criteria and completed Characterization Visit procedures.
- Met criteria for hypocholesterolemia in ASD.
- Subject continues to meet double-blind, placebo-controlled trial phase inclusion criteria.
- Biological parent(s) and full or half-sibling(s) of any age.
Who cannot join
- Known pregnancy.
- Subject has SLOS or known cholesterol synthesis/regulation disorder.
- The subject has had an anticonvulsant dose change in the preceding 3 months or a seizure in the preceding 3 months.
- DSM-IV diagnosis of Rett Disorder, childhood disintegrative disorder, schizophrenia, another psychotic disorder, or substance abuse.
- A significant medical condition such as heart disease, hypertension, liver or renal failure, pulmonary disease, diabetes, or unstable seizure disorder identified by history, physical examination, or laboratory tests.
- Dietary supplementation doses, including megavitamins, have changed within the preceding 3 months.
Show all 23Show fewer
- Currently on or has taken a statin or other medication meant to lower cholesterol within the preceding 3 months.
- Currently on or has taken dietary cholesterol supplementation within the preceding 3 months.
- Subjects will be excluded if they are on other medications or supplements that affect cholesterol or other lipid levels.
- Subjects with gastronomy feeding tubes (G-tubes) will be excluded.
- Subjects for whom English is not the primary language will be excluded.
- (No subjects will be excluded based on race, ethnicity or gender).
- Characterization Visit:
- Same exclusion criteria as the Screening Visit.
- Allergy to lanolin or soy (Hypo+ASD only).
- Non-verbal mental age below 18 months as measured by the developmentally-appropriate form of the Stanford-Binet-V, Differential Abilities Scale, or the Mullen Scales of Early Learning (N.B. potential subjects who test below 18 months of age, but are otherwise eligible, may be admitted to the study following a case review convened by the Multisite Steering Committee).
- Did not meet the criteria for an ASD during the Characterization Visit.
- 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 started a neuroleptic medication or medication that affects cholesterol synthesis or metabolism.
- Family Members of ASD+Hypo only:
- Those individuals not willing to provide a blood sample or a saliva sample for DNA.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Cholesterol in Autism Spectrum Disorder (ASD): Characterization and Treatment
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.
Read more
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.
Read the 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.
- Conditions
- Autism, Asperger Disorder, PDD-NOS
- Being tested
- Cholesterol
- Keywords
- Autism, Autism Spectrum Disorder, Cholesterol, Smith-Lemli-Opitz Syndrome, ASD, Pervasive Developmental Disorder, PPD-NOS
- Medical subject headings
- Autistic Disorder, Asperger Syndrome, Autism Spectrum Disorder, Smith-Lemli-Opitz Syndrome, Child Development Disorders, Pervasive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CholesterolOther
What is being measured
The primary outcome is the main question the study is designed to answer.
Behavioral Changes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2009 (estimated)
- Study start28 Jul 2009
- Study completion14 Nov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for AutismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Forbes D Porter, M.D., Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00965068
- Sponsor's protocol ID
- 090203
- Other IDs
- 09-CH-0203
- Status last verified
- 8 Jun 2015
- First submitted
- 24 Aug 2009
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
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.
PubMed 9024565Elias 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.
PubMed 9024564Kaufmann WE, Cortell R, Kau AS, Bukelis I, Tierney E, Gray RM, Cox C, Capone GT, Stanard P. Autism spectrum disorder in fragile X syndrome: communication, social interaction, and specific behaviors. Am J Med Genet A. 2004 Sep 1;129A(3):225-34. doi: 10.1002/ajmg.a.30229.
PubMed 15326621
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cholesterol in Autism Spectrum Disorder (ASD): Characterization and Treatment
- ClinicalTrials.gov ID
- NCT00965068
- Acronym / sponsor ID
- 090203
- Conditions
- Autism, Asperger Disorder, PDD-NOS
- Keywords
- Autism, Autism Spectrum Disorder, Cholesterol, Smith-Lemli-Opitz Syndrome, ASD, Pervasive Developmental Disorder, PPD-NOS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 28 Jul 2009
- Study completion
- 14 Nov 2013 (actual)
- First posted
- 25 Aug 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
Who may qualify
- Ages
- 4 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (16 listed)
- Parents agree to use a multivitamin with minerals if their child is selected to continue to the cholesterol supplementation clinical trial.
- Parents agree to not change the doses of other dietary supplement throughout the clinical trial, including megavitamins.
- Supplements or medications that are not meant to lower cholesterol levels but are likely to have cholesterol-lowering effects (such as Omega 3 or fish oil) will be permitted if the dose has been stable for at least 3 months prior to the initial screening visit.
- Male or female between the ages of 4.0-12.0 years at the time of consent/assent.
- Clinically diagnosed with an ASD for which no cause has been detected.
Key exclusion criteria (23 listed)
- Known pregnancy.
- Subject has SLOS or known cholesterol synthesis/regulation disorder.
- The subject has had an anticonvulsant dose change in the preceding 3 months or a seizure in the preceding 3 months.
- DSM-IV diagnosis of Rett Disorder, childhood disintegrative disorder, schizophrenia, another psychotic disorder, or substance abuse.
- A significant medical condition such as heart disease, hypertension, liver or renal failure, pulmonary disease, diabetes, or unstable seizure disorder identified by history, physical examination, or laboratory tests.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cholesterol | Other | – |
Primary outcome
Behavioral Changes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
- Background: PubMed 9024565Irons 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.
- Background: PubMed 9024564Elias 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.
- Background: PubMed 15326621Kaufmann WE, Cortell R, Kau AS, Bukelis I, Tierney E, Gray RM, Cox C, Capone GT, Stanard P. Autism spectrum disorder in fragile X syndrome: communication, social interaction, and specific behaviors. Am J Med Genet A. 2004 Sep 1;129A(3):225-34. doi: 10.1002/ajmg.a.30229.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Forbes D Porter, M.D. principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cholesterol in people with Autism and Asperger Disorder, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Behavioral Changes. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00965068, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2018.