- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00001721
Study of Smith-Lemli-Opitz Syndrome
Clinical and Basic Investigations Into Smith-Lemli-Opitz Syndrome
Smith-Lemli-Opitz Syndrome (SLOS) is a genetic disorder (autosomal recessive) caused by an abnormality in the production of cholesterol. The disorder can occur in both a "mild" or "severe" form. SLOS is associated with multiple birth defects and mental retardation. Some of the birth defects include; abnormal facial features, poor muscle tone, poor growth, shortened life span, and abnormalities of the heart, lungs, brain, gastrointestinal tract, limbs, genitalia, and kidneys.
There is no known cure for SLOS but recently patients have been treated with increased amounts of cholesterol in their diet. The cholesterol in a persons diet is unable to correct the abnormalities in the patient's organs, but researchers hope it will improve growth failure and mental retardation.
This study was developed to answer questions about the causes and complications of SLOS, as well as the effectiveness of cholesterol treatment. The study will enroll patients diagnosed with SLOS, and their mothers. The objectives of the study will be to address the following questions:
- <TAB> What is the prognosis / natural history of the demyelination in the nervous system of patients with SLOS?
- <TAB> Do patients with SLOS have other problems concerning the function of their endocrine systems?
- <TAB>What are the genetic make-ups of patients with SLOS?
- <TAB>Can further studies of cholesterol metabolism and genetic testing, using SLOS fibroblasts, increase the understanding of SLOS?<TAB>
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Maryland
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Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
- INCLUSION CRITERIA:
- Any patient with biochemically confirmed SLOS will be accepted into this study. Patients of any age, either gender, or any ethnicity will be accepted into this study. No exclusions will be made based on race or gender. Historically, more males than females have been diagnosed as having SLOS. This bias was likely a result of the fact that genital hypoplasia is readily apparent in a male, and therefore the clinical diagnosis is easier to make in a male patient. SLOS syndrome appears more commonly in individuals of Northern European ancestry. Out of 150 biochemically proven cases, only one was an African American and no patients of Asian descent were reported. One SLOS mutant allele (R404C) appears to be present in individuals of French Canadian and Creole heritage. This likely represents a founder effect. One puzzling finding is that the carrier rate of the most common SLOS mutant allele in Black Canadians from Ontario and African Americans from Pennsylvania appears to be approximately 0.7%. However, clinical cases appear to be rare. The predominance of Caucasians reported in the literature may represent a bias of ascertainment of the disorder, variable presentation in different ethnic groups, or a founder effect in some ethnic groups. Because we function as a referral center with respect to recruitment, the ethnic background of our population is likely going to reflect the overall population of diagnosed cases.
EXCLUSION CRITERIA:
- Patients will be excluded if they cannot travel to the NIH because of their medical condition.
- Pregnant women will be excluded, and a negative urine pregnancy test will be required of menstruating women. This protocol focuses on biosampling. Increasing blood draws during pregnancy for research is not appropriate. Fetuses will be excluded since the proposed evaluations are not possible during fetal life.
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
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Patients
Patients diagnosed with SLOS
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Neurocognitive Evalustion
Time Frame: Yearly
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Stabilization
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Yearly
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Collaborators and Investigators
Investigators
- Principal Investigator: Samar N Rahhal, M.D., Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Publications and helpful links
General 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.
- 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.
- Opitz JM. RSH/SLO ("Smith-Lemli-Opitz") syndrome: historical, genetic, and developmental considerations. Am J Med Genet. 1994 May 1;50(4):344-6. doi: 10.1002/ajmg.1320500408.
- Thurm A, Tierney E, Farmer C, Albert P, Joseph L, Swedo S, Bianconi S, Bukelis I, Wheeler C, Sarphare G, Lanham D, Wassif CA, Porter FD. Development, behavior, and biomarker characterization of Smith-Lemli-Opitz syndrome: an update. J Neurodev Disord. 2016 Apr 5;8:12. doi: 10.1186/s11689-016-9145-x. eCollection 2016.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Metabolic Diseases
- Disease
- Urogenital Abnormalities
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Musculoskeletal Diseases
- Stomatognathic Diseases
- Mouth Diseases
- Bone Diseases
- Metabolism, Inborn Errors
- Lipid Metabolism Disorders
- Dyslipidemias
- Mouth Abnormalities
- Stomatognathic System Abnormalities
- Jaw Abnormalities
- Jaw Diseases
- Maxillofacial Abnormalities
- Craniofacial Abnormalities
- Musculoskeletal Abnormalities
- Abnormalities, Multiple
- Lipid Metabolism, Inborn Errors
- Bone Diseases, Developmental
- Steroid Metabolism, Inborn Errors
- Penile Diseases
- Craniofacial Dysostosis
- Dysostoses
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Genital Diseases, Male
- Genital Diseases
- Syndrome
- Cleft Palate
- Hypospadias
- Genetic Diseases, X-Linked
- Smith-Lemli-Opitz Syndrome
- Hypertelorism
Other Study ID Numbers
- 980081
- 98-CH-0081
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Smith-Lemli-Opitz Syndrome
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Northwestern UniversityWithdrawnCHILD Syndrome | Smith Lemli Opitz Syndrome | Syndromic Ichthyoses | Conradi Syndrome
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Eunice Kennedy Shriver National Institute of Child...RecruitingCHILD Syndrome | Smith Lemli Opitz Syndrome | Lathosterolosis | DesmosterolosisUnited States
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Oregon Health and Science UniversityNational Heart, Lung, and Blood Institute (NHLBI)TerminatedSmith-Lemli-Opitz SyndromeUnited States
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Eunice Kennedy Shriver National Institute of Child...WithdrawnSmith-Lemi-Opitz Syndrome
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Oregon Health and Science UniversityTerminatedSmith-Lemli-Opitz SyndromeUnited States
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Eunice Kennedy Shriver National Institute of Child...CompletedPregnancy | Smith-Lemli-Opitz SyndromeUnited States
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National Center for Research Resources (NCRR)Oregon Health and Science UniversityUnknownSmith-Lemli-Opitz SyndromeUnited States
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Eunice Kennedy Shriver National Institute of Child...CompletedSmith-Lemli-Opitz SyndromeUnited States
-
Eunice Kennedy Shriver National Institute of Child...CompletedEstimation of the Carrier Frequency and Incidence of Smith-Lemli-Opitz Syndrome in African AmericansSmith-Lemli-Opitz SyndromeUnited States
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Boston Children's HospitalCompletedSmith-Lemli-Opitz SyndromeUnited States
Clinical Trials on Cholesterol Suspension
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Boston Children's HospitalCompletedSmith-Lemli-Opitz SyndromeUnited States
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Azienda Ospedaliero, Universitaria PisanaCompleted
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Wake Forest University Health SciencesWithdrawn
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University of Colorado, DenverRecruitingHearing Loss | Smith-Lemli-Opitz Syndrome | Cone-Rod DystrophyUnited States
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Perrigo CSCIAnalyze & RealizeRecruitingBlood Cholesterol Lowers | LDL-CGermany
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Eunice Kennedy Shriver National Institute of Child...CompletedAutism | Asperger Disorder | PDD-NOSUnited States
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Eunice Kennedy Shriver National Institute of Child...CompletedSmith-Lemli-Opitz SyndromeUnited States
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University of PennsylvaniaBristol-Myers SquibbCompleted
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Navigen, Inc.National Institute of Allergy and Infectious Diseases (NIAID); CovanceCompleted
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University of PennsylvaniaAstraZenecaCompleted