Smith-Lemi-Opitz SyndromeNCT01413425
A Long-Term Study of Cholesterol Supplements for Smith-Lemli-Opitz Syndrome
An observational study of Smith-Lemi-Opitz Syndrome, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
Trial summary
Background: Smith-Lemli-Opitz syndrome (SLOS) is a genetic disorder that prevents the body from making enough cholesterol. People who have SLOS often need to take extra cholesterol, either in food or in supplements, for their bodies to work properly. Cholesterol is very important for the brain and nervous system. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Smith-Lemi-Opitz Syndrome
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 29 Jun 2011to 20 Oct 2014
- Phase
- Observational
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The population being studied is subjects with SLOS. Children will not be excluded, in fact, the majority of subjects being studied will be infants and children. Relatively few adults with SLOS are known. We will continue to recruit subjects of all ages from newborn to adult of both genders.
- Women and girls will certainly be included in the study. Women should be equally represented in this study. SLOS is an autosomal recessively inherited condition that affects males and females equally. However, since these disorders are uncommon autosomal-recessively inherited inborn errors of metabolism, STAIR investigators will have limited control over the gender mix of the study population.
- As mentioned for gender, STAIR investigators will have limited control over the race and ethnicity mix of the study population. In order to increase the enrollment of minority subjects, with permission, we will inform the national disease support group of our studies so that subjects in other regions of the US with ethnically and racially more diverse populations may be recruited. SLOS seems to be most common in Caucasians. In the current SLOS study at OHSU, only one of the 34 SLOS subjects is Hispanic. There is only 1 report of carriers in Blacks (Nowaczyk, 2001) and only 31 cases reported in a Japanese survey. In Oregon at least, we will advertise the study at local community health clinics where large numbers of Hispanics are seen.
Who cannot join
- None.
About this study
Official title: Smith-Lemli-Opitz Syndrome: A Longitudinal Clinical Study of Patients Receiving Cholesterol Supplementation
Background:
- Smith-Lemli-Opitz syndrome (SLOS) is a genetic disorder that prevents the body from making enough cholesterol. People who have SLOS often need to take extra cholesterol, either in food or in supplements, for their bodies to work properly. Cholesterol is very important for the brain and nervous system. Therefore SLOS is highly related to autism, mental retardation, and other brain and nervous system disorders. Not much is known about how people with SLOS handle cholesterol and how taking extra cholesterol helps them. A long-term study of people with SLOS will help answer these and other questions.
Read more
Objectives:
- To study the effects of a high-cholesterol diet on people with Smith-Lemli-Opitz syndrome.
Eligibility:
- Individuals of any age who have Smith-Lemli-Opitz syndrome.
Design:
- Participants will have study visits up to two times in the first year and once a year every year after that. Each visit will last between 3 and 5 days.
- Participants will be screened with a physical exam, medical history, and blood and urine tests.
- Participants will provide regular blood, urine, stool, saliva, and skin cell samples for testing.
- Participants will keep track of the foods they eat at home. During the study, they will eat a high-cholesterol diet at all times, except for the second study visit (3 to 6 months after the screening visit). That visit will involve a cholesterol-free diet for 4 weeks.
- Participants will have special cholesterol tests with blood samples at different times during the study.
- At different study visits, participants will have tests of mental and physical skills (including tests for autism). They will answer questions about their diet and food habits. They will also have hearing and eye tests, body and bone measurements, and imaging studies. Not all of the tests will be done at every study.
- Participants will be allowed to leave the study at any time.
Read the detailed description
The purpose of this study is to learn as much as possible about Smith-Lemli-Opitz Syndrome (SLOS) by following a large group of individuals with SLOS over a period of time. We plan to measure cholesterol and other sterol levels, perform clinical observations, whole body testing and imaging studies (brain MRIs), to learn more about disease mechanisms and progression, variations in the clinical features among individuals with SLOS, and evaluate the effect of cholesterol supplementation in this condition.
Smith-Lemli-Opitz syndrome (SLOS) is a disorder of cholesterol synthesis, or production. It is caused by mutations in the DHCR7 gene which encodes for 7-dehydrocholesterol reductase, an enzyme necessary for the production of cholesterol in the body. Affected individuals exhibit multiple malformations and mental retardation. The features of SLOS are thought to be primarily related to cholesterol deficiency and accumulation of cholesterol precursors. However, the clinical phenotype is not well characterized, the biochemical pathogenesis is incompletely understood, and there is no proven therapy for this devastating condition. Thus our primary objective is to better define the clinical and biochemical phenotypes of the disease using a natural history study design. The study will contribute to creating a comprehensive SLOS patient registry, identify biomarkers that can be used for diagnostic testing, screening and outcome measures in future therapeutic trials. All patients with SLOS receive dietary cholesterol supplementation with the hope that cholesterol supplementation will improve the clinical manifestation of the disease. However, there is no evidence supporting a clinical benefit of cholesterol supplementation. Thus a secondary objective of the study is to determine if cholesterol intake correlates with changes in whole body cholesterol homeostasis and clinical end-points.
- Conditions
- Smith-Lemi-Opitz Syndrome
- Keywords
- Smith-Lemli-Opitz Syndrome, Cholesterol, SLOS
- Medical subject headings
- Smith-Lemli-Opitz Syndrome
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2011 (estimated)
- Study start29 Jun 2011
- Study completion20 Oct 2014
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 Smith-Lemi-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
- Observational
- Time perspective
- Other
- Enrolment
- 0 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
- 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
- NCT01413425
- Sponsor's protocol ID
- 110194
- Other IDs
- 11-CH-0194
- Status last verified
- 20 Oct 2014
- First submitted
- 9 Aug 2011
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
SMITH DW, LEMLI L, OPITZ JM. A NEWLY RECOGNIZED SYNDROME OF MULTIPLE CONGENITAL ANOMALIES. J Pediatr. 1964 Feb;64:210-7. doi: 10.1016/s0022-3476(64)80264-x. No abstract available.
PubMed 14119520Cunniff C, Kratz LE, Moser A, Natowicz MR, Kelley RI. Clinical and biochemical spectrum of patients with RSH/Smith-Lemli-Opitz syndrome and abnormal cholesterol metabolism. Am J Med Genet. 1997 Jan 31;68(3):263-9.
PubMed 9024557Ryan AK, Bartlett K, Clayton P, Eaton S, Mills L, Donnai D, Winter RM, Burn J. Smith-Lemli-Opitz syndrome: a variable clinical and biochemical phenotype. J Med Genet. 1998 Jul;35(7):558-65. doi: 10.1136/jmg.35.7.558.
PubMed 9678700
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Smith-Lemli-Opitz Syndrome: A Longitudinal Clinical Study of Patients Receiving Cholesterol Supplementation
- ClinicalTrials.gov ID
- NCT01413425
- Acronym / sponsor ID
- 110194
- Conditions
- Smith-Lemi-Opitz Syndrome
- Keywords
- Smith-Lemli-Opitz Syndrome, Cholesterol, SLOS
- Study type
- Observational
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 29 Jun 2011
- Study completion
- 20 Oct 2014
- First posted
- 10 Aug 2011 (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:
- Smith-Lemli-Opitz syndrome (SLOS) is a genetic disorder that prevents the body from making enough cholesterol. People who have SLOS often need to take extra cholesterol, either in food or in supplements, for their bodies to work properly. Cholesterol is very important for the brain and nervous system. Therefore SLOS is highly related to autism, mental retardation, and other brain and nervous system disorders. Not much is known about how people with SLOS handle cholesterol and how taking extra cholesterol helps them. A long-term study of people with SLOS will help answer these and other questions.
Objectives:
- To study the effects of a high-cholesterol diet on people with Smith-Lemli-Opitz syndrome.
Eligibility:
- Individuals of any age who have Smith-Lemli-Opitz syndrome.
Design:
- Participants will have study visits up to two times in the first year and once a year every year after that. Each visit will last between 3 and 5 days.
- Participants will be screened with a physical exam, medical history, and blood and urine tests.
- Participants will provide regular blood, urine, stool, saliva, and skin cell samples for testing.
- Participants will keep track of the foods they eat at home. During the study, they will eat a high-cholesterol diet at all times, except for the second study visit (3 to 6 months after the screening visit). That visit will involve a cholesterol-free diet for 4 weeks.
- Participants will have special cholesterol tests with blood samples at different times during the study.
- At different study visits, participants will have tests of mental and physical skills (including tests for autism). They will answer questions about their diet and food habits. They will also have hearing and eye tests, body and bone measurements, and imaging studies. Not all of the tests will be done at every study.
- Participants will be allowed to leave the study at any time.
Detailed description
The purpose of this study is to learn as much as possible about Smith-Lemli-Opitz Syndrome (SLOS) by following a large group of individuals with SLOS over a period of time. We plan to measure cholesterol and other sterol levels, perform clinical observations, whole body testing and imaging studies (brain MRIs), to learn more about disease mechanisms and progression, variations in the clinical features among individuals with SLOS, and evaluate the effect of cholesterol supplementation in this condition.
Smith-Lemli-Opitz syndrome (SLOS) is a disorder of cholesterol synthesis, or production. It is caused by mutations in the DHCR7 gene which encodes for 7-dehydrocholesterol reductase, an enzyme necessary for the production of cholesterol in the body. Affected individuals exhibit multiple malformations and mental retardation. The features of SLOS are thought to be primarily related to cholesterol deficiency and accumulation of cholesterol precursors. However, the clinical phenotype is not well characterized, the biochemical pathogenesis is incompletely understood, and there is no proven therapy for this devastating condition. Thus our primary objective is to better define the clinical and biochemical phenotypes of the disease using a natural history study design. The study will contribute to creating a comprehensive SLOS patient registry, identify biomarkers that can be used for diagnostic testing, screening and outcome measures in future therapeutic trials. All patients with SLOS receive dietary cholesterol supplementation with the hope that cholesterol supplementation will improve the clinical manifestation of the disease. However, there is no evidence supporting a clinical benefit of cholesterol supplementation. Thus a secondary objective of the study is to determine if cholesterol intake correlates with changes in whole body cholesterol homeostasis and clinical end-points.
Study design
- Time perspective
- Other
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- The population being studied is subjects with SLOS. Children will not be excluded, in fact, the majority of subjects being studied will be infants and children. Relatively few adults with SLOS are known. We will continue to recruit subjects of all ages from newborn to adult of both genders.
- Women and girls will certainly be included in the study. Women should be equally represented in this study. SLOS is an autosomal recessively inherited condition that affects males and females equally. However, since these disorders are uncommon autosomal-recessively inherited inborn errors of metabolism, STAIR investigators will have limited control over the gender mix of the study population.
- As mentioned for gender, STAIR investigators will have limited control over the race and ethnicity mix of the study population. In order to increase the enrollment of minority subjects, with permission, we will inform the national disease support group of our studies so that subjects in other regions of the US with ethnically and racially more diverse populations may be recruited. SLOS seems to be most common in Caucasians. In the current SLOS study at OHSU, only one of the 34 SLOS subjects is Hispanic. There is only 1 report of carriers in Blacks (Nowaczyk, 2001) and only 31 cases reported in a Japanese survey. In Oregon at least, we will advertise the study at local community health clinics where large numbers of Hispanics are seen.
Key exclusion criteria (1 listed)
- None.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 14119520SMITH DW, LEMLI L, OPITZ JM. A NEWLY RECOGNIZED SYNDROME OF MULTIPLE CONGENITAL ANOMALIES. J Pediatr. 1964 Feb;64:210-7. doi: 10.1016/s0022-3476(64)80264-x. No abstract available.
- Background: PubMed 9024557Cunniff C, Kratz LE, Moser A, Natowicz MR, Kelley RI. Clinical and biochemical spectrum of patients with RSH/Smith-Lemli-Opitz syndrome and abnormal cholesterol metabolism. Am J Med Genet. 1997 Jan 31;68(3):263-9.
- Background: PubMed 9678700Ryan AK, Bartlett K, Clayton P, Eaton S, Mills L, Donnai D, Winter RM, Burn J. Smith-Lemli-Opitz syndrome: a variable clinical and biochemical phenotype. J Med Genet. 1998 Jul;35(7):558-65. doi: 10.1136/jmg.35.7.558.
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)
Questions about this trial
What is this clinical trial studying?
An observational study of Smith-Lemi-Opitz Syndrome, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
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 1 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: withdrawn, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01413425, 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 2 Jul 2017.