Smith-Lemli-Opitz SyndromePhase 2NCT00114634
Short-term Behavioral Effects of Cholesterol Therapy in Smith-Lemli-Opitz Syndrome
A Phase 2 study testing Egg yolk preparation with cholesterol and Egg substitute, without cholesterol in people with Smith-Lemli-Opitz Syndrome, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
This 10-week study will evaluate and compare behavior changes in children with Smith-Lemli-Opitz syndrome (SLOS) who are taking cholesterol supplementation versus those who are not on cholesterol supplementation. SLOS is a genetic disorder that affects the development of children both before and after birth. Read more about this study
- Who is it for?
- Ages 4 to 17 years
- Conditions the study is for
- Smith-Lemli-Opitz Syndrome
- What is being tested?
- Egg yolk preparation with cholesterol and Egg substitute, without cholesterol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2005to Feb 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- This study will include pediatric patients, ages 4-17 years old with a biochemical diagnosis of Smith-Lemli-Opitz Syndrome (SLOS).
- Only mild and classical patients will be enrolled.
- This study will be open to include SLOS patients regardless of whether or not they are participating in another NIH protocol.
Who cannot join
- Patients with a history of egg allergy or intolerance will be excluded from this study.
- Subjects must be well enough to be in a home setting.
- Patients participating in our simvastatin protocol (03-CH-3225) will be excluded from this study.
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: Short-Term Behavioral Effects of Cholesterol Therapy in Smith-Lemli-Opitz Syndrome
This 10-week study will evaluate and compare behavior changes in children with Smith-Lemli-Opitz syndrome (SLOS) who are taking cholesterol supplementation versus those who are not on cholesterol supplementation. SLOS is a genetic disorder that affects the development of children both before and after birth. An enzyme deficiency in these children results in low levels of cholesterol, which can cause a variety of birth defects and behavioral problems. Typical abnormal physical features of patients include a small head, drooping eyelids, small upturned nose, small chin, cleft palate, heart defects, and extra fingers or toes.
Children between 5 and 17 with mild SLOS who do not have a history of egg allergy or intolerance may be eligible for this study. Candidates are screened with a questionnaire about the patient's age, genotype (if known), sterol levels, symptoms, current treatment and medical history.
Read more
Children participate in two 2-week study phases. Between the study phases the children will take 150 mg/kg daily of a cholesterol preparation typically used to supplement cholesterol in patients in SLOS studies at NIH. In the study phases, the participants are randomly assigned to take either egg yolk or an egg yolk substitute, such as Egg Beaters, that does not contain cholesterol. The study is done at the participant's home, and the cholesterol supplementation and egg/egg substitute are sent to the home each day with instructions on how to take them.
The caretakers can stop the study phases after four days if behavior problems occur.
The children's caretakers fill out a standard behavioral questionnaire, the Aberrant Behavior Checklist. The questionnaire is designed to assess the effects of treatment in mentally impaired persons.
Read the detailed description
Smith-Lemli- Opitz syndrome (SLOS) is an autosomal recessive genetic condition caused by a deficiency of the enzyme 3beta-hydroxysterol delta(7)- reductase (DHCR7). DHCR7 is the final enzyme in the sterol synthetic pathway and converts 7- dehydrocholesterol (7DHC) to cholesterol. This results in low cholesterol and elevated 7DHC levels. SLOS has a wide phenotypic spectrum. Mildly affected individuals may have subtle dysmorphic features along with learning and behavioral disabilities. Typical clinical manifestations include microcephaly, ptosis, anteversion of the nostrils, micrognathia, high arched or cleft palate, congenital heart defects, clinodactyly, post- axial polydactyly, and 2-3 toe syndactyly. More severely affected individuals have multiple congenital anomalies, may be miscarried, stillborn, or die within the first few weeks of life.
Dietary cholesterol supplementation in children with SLOS is reported to improve behavior, growth and nutritional status. Based upon observational studies, the behavioral changes reported with dietary cholesterol supplementation occur rapidly and appear to be reversible. Parental reports of improved behavior could be influenced by a placebo effect. Thus, we are proposing a blinded study to compare behavioral changes while the patient is on cholesterol supplementation (egg yolk) versus no cholesterol supplementation (egg substitute).
The objectives of this study are:
- To quantitatively evaluate behavior, in a blinded study, of SLOS children on and off dietary cholesterol supplementation.
- To quantitatively evaluate behavior in SLOS children treated with egg yolk compared to synthetic dietary cholesterol supplementation.
Completed study has been published. Tierney, E., Conley, S.K., Goodwin, H., Porter, F.D. (2010) Analysis of short-term behavioral effects of dietary cholesterol supplementation in Smith-Lemli-Opitz Syndrome. Am. J. Med. Genet. Part A. 152A: 91-95 PMID: 20014133
- Conditions
- Smith-Lemli-Opitz Syndrome
- Being tested
- Egg yolk preparation with cholesterol, Egg substitute, without cholesterol
- Keywords
- SLOS, RSH syndrome, ABC Checklist, Cholesterol supplementation, Egg yolk, Smith-Lemli-Opitz Syndrome
- Medical subject headings
- Smith-Lemli-Opitz Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Egg yolk preparation with cholesterolDietary supplement
Egg yolk preparation with cholesterol
Egg substitute, without cholesterolDietary supplement
Placebo control. Egg substitute, without cholesterol
| Study group | Role | What they receive |
|---|---|---|
| Egg yolk preparation with cholesterol | Experimental | Dietary cholesterol in the form of liquid egg yolk Receives: Dietary Supplement: Egg yolk preparation with cholesterol |
| Egg yolk preparation without cholesterol | Placebo comparator | No dietary cholesterol supplementation (egg substitute) Papetti Foods "Better 'n Eggs" egg substitute Receives: Dietary Supplement: Egg substitute, without cholesterol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hyperactivity Sub-scale of the Aberrant Behavior Checklist-Community (ABC-C).
The Aberrant Behavior Checklist-Community (ABC-C) is a measure used to identify treatment efficacy among intellectually impaired individuals. ABC Subscale IV (Hyperactivity) has 16 items, each can be rated from 0 to 3, with 0 equal to not at all a problems, one the problem is the behavior but slight in degree, to the problem is moderately serious, 3 the problem is severe in degree. For this subscale, score can go from 0 - 48. The higher the score, the worse the hyperactivity. The comparison in this study was made between the blinded phases when patients received either egg yolk (treated, +cholesterol) or egg substitute (untreated, -cholesterol). Order was randomized.
Measured: 2 weeks
Secondary outcomes (5)
ABC Irritability Sub-scale
ABC Subscale I (Irritability) has 15 items, each can be rated from 0 to 3, with 0 equal to not at all a problem, 1 the problem is the behavior but slight in degree, 2 the problem is moderately serious, 3 the problem is severe in degree. For this subscale, score can go from 0 - 45
Measured: 2 weeks
ABC Lethargy Sub-scale
ABC Subscale II (Lethargy) has 16 items, each can be rated from 0 to 3, with 0 equal to not at all a problems, 1 the problem is the behavior but slight in degree,2 the problem is moderately serious, 3 the problem is severe in degree. For this subscale, score can go from 0 - 48.
Measured: 2 weeks
ABC Stereotypy Sub-scale
ABC Subscale III (Stereotypy) has 7 items, each can be rated from 0 to 3, with 0 equal to not at all a problems, 1 the problem is the behavior but slight in degree, 2 the problem is moderately serious, 3 the problem is severe in degree. For this subscale, score can go from 0 - 21.
Measured: 2 weeks
ABC Inappropriate Behavior Sub-scale
ABC Subscale V (Inappropriate speech) has 4 items, each can be rated from 0 to 3, with 0 equal to not at all a problems, 1 the problem is the behavior but slight in degree, 2 the problem is moderately serious, 3 the problem is severe in degree. For this subscale, score can go from 0 - 12.
Measured: 2 weeks
ABC Total Score
ABC total score includes all the questions from subscales, with range of 0 to 174. Higher the score , the greater the problem.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2005 (estimated)
- Study startJun 2005
- Primary completionFeb 2009
- Study completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Smith-Lemli-Opitz SyndromeStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 13 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
- Principal investigator, Forbes Porter, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Forbes D Porter, MD, Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00114634
- Sponsor's protocol ID
- 050168
- Other IDs
- 05-CH-0168
- Status last verified
- Dec 2015
- First submitted
- 15 Jun 2005
- Last updated
- 29 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 9024564Irons 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 9024565Kelley RI. A new face for an old syndrome. Am J Med Genet. 1997 Jan 31;68(3):251-6. doi: 10.1002/(sici)1096-8628(19970131)68:33.0.co;2-p. No abstract available.
PubMed 9024554
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short-Term Behavioral Effects of Cholesterol Therapy in Smith-Lemli-Opitz Syndrome
- ClinicalTrials.gov ID
- NCT00114634
- Acronym / sponsor ID
- 050168
- Conditions
- Smith-Lemli-Opitz Syndrome
- Keywords
- SLOS, RSH syndrome, ABC Checklist, Cholesterol supplementation, Egg yolk, Smith-Lemli-Opitz Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- Jun 2005
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 16 Jun 2005 (estimated)
- Results
- Posted 9 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This 10-week study will evaluate and compare behavior changes in children with Smith-Lemli-Opitz syndrome (SLOS) who are taking cholesterol supplementation versus those who are not on cholesterol supplementation. SLOS is a genetic disorder that affects the development of children both before and after birth. An enzyme deficiency in these children results in low levels of cholesterol, which can cause a variety of birth defects and behavioral problems. Typical abnormal physical features of patients include a small head, drooping eyelids, small upturned nose, small chin, cleft palate, heart defects, and extra fingers or toes.
Children between 5 and 17 with mild SLOS who do not have a history of egg allergy or intolerance may be eligible for this study. Candidates are screened with a questionnaire about the patient's age, genotype (if known), sterol levels, symptoms, current treatment and medical history.
Children participate in two 2-week study phases. Between the study phases the children will take 150 mg/kg daily of a cholesterol preparation typically used to supplement cholesterol in patients in SLOS studies at NIH. In the study phases, the participants are randomly assigned to take either egg yolk or an egg yolk substitute, such as Egg Beaters, that does not contain cholesterol. The study is done at the participant's home, and the cholesterol supplementation and egg/egg substitute are sent to the home each day with instructions on how to take them.
The caretakers can stop the study phases after four days if behavior problems occur.
The children's caretakers fill out a standard behavioral questionnaire, the Aberrant Behavior Checklist. The questionnaire is designed to assess the effects of treatment in mentally impaired persons.
Detailed description
Smith-Lemli- Opitz syndrome (SLOS) is an autosomal recessive genetic condition caused by a deficiency of the enzyme 3beta-hydroxysterol delta(7)- reductase (DHCR7). DHCR7 is the final enzyme in the sterol synthetic pathway and converts 7- dehydrocholesterol (7DHC) to cholesterol. This results in low cholesterol and elevated 7DHC levels. SLOS has a wide phenotypic spectrum. Mildly affected individuals may have subtle dysmorphic features along with learning and behavioral disabilities. Typical clinical manifestations include microcephaly, ptosis, anteversion of the nostrils, micrognathia, high arched or cleft palate, congenital heart defects, clinodactyly, post- axial polydactyly, and 2-3 toe syndactyly. More severely affected individuals have multiple congenital anomalies, may be miscarried, stillborn, or die within the first few weeks of life.
Dietary cholesterol supplementation in children with SLOS is reported to improve behavior, growth and nutritional status. Based upon observational studies, the behavioral changes reported with dietary cholesterol supplementation occur rapidly and appear to be reversible. Parental reports of improved behavior could be influenced by a placebo effect. Thus, we are proposing a blinded study to compare behavioral changes while the patient is on cholesterol supplementation (egg yolk) versus no cholesterol supplementation (egg substitute).
The objectives of this study are:
- To quantitatively evaluate behavior, in a blinded study, of SLOS children on and off dietary cholesterol supplementation.
- To quantitatively evaluate behavior in SLOS children treated with egg yolk compared to synthetic dietary cholesterol supplementation.
Completed study has been published. Tierney, E., Conley, S.K., Goodwin, H., Porter, F.D. (2010) Analysis of short-term behavioral effects of dietary cholesterol supplementation in Smith-Lemli-Opitz Syndrome. Am. J. Med. Genet. Part A. 152A: 91-95 PMID: 20014133
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Egg yolk preparation with cholesterol | Experimental | Dietary Supplement: Egg yolk preparation with cholesterolDietary cholesterol in the form of liquid egg yolk |
| Egg yolk preparation without cholesterol | Placebo comparator | Dietary Supplement: Egg substitute, without cholesterolNo dietary cholesterol supplementation (egg substitute) Papetti Foods "Better 'n Eggs" egg substitute |
Who may qualify
- Ages
- 4 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- This study will include pediatric patients, ages 4-17 years old with a biochemical diagnosis of Smith-Lemli-Opitz Syndrome (SLOS).
- Only mild and classical patients will be enrolled.
- This study will be open to include SLOS patients regardless of whether or not they are participating in another NIH protocol.
Key exclusion criteria (3 listed)
- Patients with a history of egg allergy or intolerance will be excluded from this study.
- Subjects must be well enough to be in a home setting.
- Patients participating in our simvastatin protocol (03-CH-3225) will be excluded from this study.
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 |
|---|---|---|
| Egg yolk preparation with cholesterolEgg yolk preparation with cholesterol | Dietary supplement | Egg yolk preparation with cholesterol |
| Egg substitute, without cholesterolPlacebo control. Egg substitute, without cholesterol | Dietary supplement | Egg yolk preparation without cholesterol |
Primary outcome
Hyperactivity Sub-scale of the Aberrant Behavior Checklist-Community (ABC-C).
Time frame: 2 weeks
The Aberrant Behavior Checklist-Community (ABC-C) is a measure used to identify treatment efficacy among intellectually impaired individuals. ABC Subscale IV (Hyperactivity) has 16 items, each can be rated from 0 to 3, with 0 equal to not at all a problems, one the problem is the behavior but slight in degree, to the problem is moderately serious, 3 the problem is severe in degree. For this subscale, score can go from 0 - 48. The higher the score, the worse the hyperactivity. The comparison in this study was made between the blinded phases when patients received either egg yolk (treated, +cholesterol) or egg substitute (untreated, -cholesterol). Order was randomized.
5 secondary outcomes
ABC Irritability Sub-scale
Time frame: 2 weeks
ABC Lethargy Sub-scale
Time frame: 2 weeks
ABC Stereotypy Sub-scale
Time frame: 2 weeks
ABC Inappropriate Behavior Sub-scale
Time frame: 2 weeks
ABC Total Score
Time frame: 2 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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 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 9024554Kelley RI. A new face for an old syndrome. Am J Med Genet. 1997 Jan 31;68(3):251-6. doi: 10.1002/(sici)1096-8628(19970131)68:33.0.co;2-p. No abstract available.
Related trials for Smith-Lemli-Opitz Syndrome
RecruitingObservational study
Biochemical and Phenotypical Aspects of Smith-Lemli-Opitz Syndrome and Related Disorders of Cholesterol Metabolism
Smith Lemli Opitz Syndrome, CHILD Syndrome
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
Not yet recruitingPhase 2/3
Double-Blind Trial of Everolimus for Improving Social Abilities in PTEN Germline Mutations
Cowden's Disease, Cowden's Syndrome
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, MD 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 2 study testing Egg yolk preparation with cholesterol and Egg substitute, without cholesterol in people with Smith-Lemli-Opitz Syndrome, 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 3 inclusion and 3 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 29 Jan 2016. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
Yes. Results are posted in the registry (first posted 9 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Hyperactivity Sub-scale of the Aberrant Behavior Checklist-Community (ABC-C). (time frame: 2 weeks). 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 NCT00114634, 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 29 Jan 2016.