Biochemical and Phenotypical Aspects of Smith-Lemli-Opitz Syndrome and Related Disorders of Cholesterol Metabolism
NCT ID: NCT05047354
Last Updated: 2025-09-08
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
250 participants
OBSERVATIONAL
2021-06-23
2031-05-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Smith-Lemli-Opitz Syndrome (SLOS) is a genetic disorder. It can cause birth defects and developmental delays. There is no cure for SLOS or other inherited diseases related to cholesterol production or storage. The data gained in this study may help researchers find ways to measure how well future treatments work.
Objective:
To learn more about SLOS and related disorders and how these diseases affect participants and relatives.
Eligibility:
People of any age who have or are suspected to have SLOS or another inherited disease related to cholesterol production or storage. Relatives are also needed.
Design:
Participants will be screened with a medical record review.
Participants will have visits every 6 to 12 months. They will have a physical exam. They will fill out a survey about their medical and behavioral history. They may have an eye exam. They may have a neurodevelopmental assessment. They may have a hearing test. Their outer and middle ears may be examined. Their ability to speak, understand speech, eat, and swallow may be assessed. They may get X-rays while they chew and swallow. Their functional ability and needs for adaptive devices or braces may be assessed. They may have a lumbar puncture. Photographs may be taken of their face and body.
Participants who cannot visit the NIH and relatives will have a virtual visit once a year. They will talk about their medical history and symptoms. They give blood, urine, and skin samples at a lab near their home. They will fill out a survey about their medical and behavioral history.
Participation will last for several years.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Study of Smith-Lemli-Opitz Syndrome
NCT00001721
Estimation of the Carrier Frequency and Incidence of Smith-Lemli-Opitz Syndrome in African Americans
NCT00017732
Prenatal Screening For Smith-Lemli-Opitz Syndrome
NCT00070850
SLOS: The Effect of Simvastatin in Patients Receiving Cholesterol Supplementation
NCT01434745
Simvastatin Therapy in Smith-Lemli-Opitz Syndrome
NCT00064792
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Our goal is to investigate genetic, biochemical, and clinical aspects of SLOS and related disorders in order to facilitate development and implementation of future therapeutic trials. This protocol consists of a main study and three sub-studies. The main study involves inperson evaluation of patients and carriers of SLOS and related disorders. The first sub-study includes collecting biorepository samples from patients and carriers of SLOS and related disorders. The second sub-study involves obtaining a telemedicine history and full review of systems for affected individuals with SLOS and related disorders. The third sub-study involves a survey of caregivers of
deceased individuals with SLOS, which will address questions regarding the deceased individual s medical history and inform causes of death. All questions in the survey will be regarding the deceased individual s medical history, none of the questions will be about the caregivers. This protocol will also maintain a database of information collected over the past two decades at the NIH on SLOS trial participants. All individuals with SLOS, related disorders and carriers will be eligible for enrollment.
Objectives: The primary objective of this study is to determine laboratory or clinical outcome measures that could be used in future therapeutic trials.
The secondary objectives of these studies are to define comorbidities and mortality of the disease, investigate the causes of mortality, identify potential participants for future therapeutic trials and evaluate possible laboratory outcome measures and biomarkers in carriers and suspected carriers.
Endpoints: Primary endpoints
1. Phenotypic characterization of individuals with SLOS and related inborn errors of cholesterol synthesis. Define and characterize disease related morbidity and mortality.
2. Establishing a biomaterial collection (Blood, urine, CSF, DNA/RNA and cell lines) corresponding to well-phenotyped individuals for biomarker discovery and characterization.
Secondary endpoints: Phenotypic history as well as blood and urine biomarkers in individuals heterozygous for pathogenic DHCR7 variants or pathogenic variants in cholesterol synthetic genes. Additional outcomes include assessments of bone health.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
COHORT
PROSPECTIVE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
1
Subjects with Smith-Lemli-Opitz syndrome
No interventions assigned to this group
2
Subjects with Disorders of cholesterol synthesis and metabolism
No interventions assigned to this group
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Clinical, biochemical, or genetic diagnosis of Smith-Lemli-Opitz Syndrome OR
* Clinical, biochemical, or genetic diagnosis of desmosterolosis, lathosterolosis, CHILD syndrome, X-linked dominant chondrodysplasia type2 or another inborn error of cholesterol synthesis OR
* Clinical suspicion of an inborn error of cholesterol synthesis, metabolism or impaired cholesterol homeostasis. Clinical observations may include, but are not limited to lipid-laden macrophages, abnormal LDL, HDL, total cholesterol, triglycerides, abnormal lipid
electrophoresis, lipid storage in other tissues. OR
-Biologic parents of affected individuals or known carriers based on previously done genetic testing who are willing and able to provide samples of any or all of the following: blood, urine, a skin biopsy, and/or tissue derived from clinically indicated surgery or autopsy.
Exclusion Criteria
* Affected individuals who, in the opinion of the investigator, are unable to comply with the protocol or have medical conditions that would potentially increase the risk of participation will be excluded from on-site participation. They may participate in the telemedicine or in the
biomaterials parts of the study.
* Carrier adults who are unable to or unwilling to provide any of the following samples: Blood, urine, skin biopsy sample or tissue derived from clinically indicated surgery or skin biopsy.
* Female participants who are pregnant will be excluded from evaluations requiring sedation, radiation and LP. Total blood draw volumes will be kept at a minimum or if anemia of pregnancy is known, no blood will be taken for research testing.
1 Day
100 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Forbes D Porter, M.D.
Role: PRINCIPAL_INVESTIGATOR
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
Role: primary
References
Explore related publications, articles, or registry entries linked to this study.
Nowaczyk MJ, Irons MB. Smith-Lemli-Opitz syndrome: phenotype, natural history, and epidemiology. Am J Med Genet C Semin Med Genet. 2012 Nov 15;160C(4):250-62. doi: 10.1002/ajmg.c.31343. Epub 2012 Oct 11.
Irons M, Elias ER, Salen G, Tint GS, Batta AK. Defective cholesterol biosynthesis in Smith-Lemli-Opitz syndrome. Lancet. 1993 May 29;341(8857):1414. doi: 10.1016/0140-6736(93)90983-n. No abstract available.
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.
Selvaraman A, Rahhal S, Bianconi S, Furnary T, Porter FD. Assessing Postnatal Mortality in Smith-Lemli-Opitz Syndrome. Am J Med Genet A. 2025 Feb;197(2):e63875. doi: 10.1002/ajmg.a.63875. Epub 2024 Sep 13.
Related Links
Access external resources that provide additional context or updates about the study.
NIH Clinical Center Detailed Web Page
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
000487-CH
Identifier Type: -
Identifier Source: secondary_id
10000487
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.