Sterol and Isoprenoid Disease Research Consortium: Smith-Lemli-Opitz Syndrome (STAIR-SLOS)

• Sponsor: Oregon Health and Science University
• Information provided by (Responsible Party): Jean-Baptiste Roullet, Oregon Health and Science University

Study Description

Brief Summary:

The purpose of this study is to learn about Smith-Lemli-Opitz Syndrome (SLOS). SLOS is an inherited condition that is caused by the body not making an enzyme as it should. The body needs the enzyme to help make cholesterol. SLOS can cause many health problems including slow growth and development, eating disorders, sleep disorders, behavior disorders, and eye diseases. Severe SLOS leads to birth defects and mental retardation and in many cases early death. The investigators plan to measure cholesterol and other sterol levels, perform clinical observations, whole body testing and imaging (brain MRIs), to learn more about the disease and its progression, differences in the clinical features among individuals with SLOS, and look at the effect of cholesterol supplementation in this condition.

The study is an interventional study to characterize disease progression and correlations between clinical, biochemical and physiological features of the disease. The main hypothesis is that dietary cholesterol supplementation does not improve features of SLOS related to the brain (e.g. IQ, behavior).

Condition or disease	Intervention/treatment	Phase
Smith-Lemli-Opitz Syndrome	Dietary Supplement: Cholesterol supplementation	Not Applicable

Detailed Description:

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- Δ7-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

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	21 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Smith-Lemli-Opitz Syndrome: A Longitudinal Clinical Study of Patients Receiving Cholesterol Supplementation
Study Start Date :	January 2011
Actual Primary Completion Date :	December 2015
Actual Study Completion Date :	December 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cholesterol supplementation; All new subjects will come to their first visit with an least 3 weeks of stable cholesterol intake. Typically and preferably this will include egg yolk as cholesterol supplement, but in some instances e.g. intolerance to egg yolk it may include a new encapsulated cholesterol preparation, Sloesterol.	Dietary Supplement: Cholesterol supplementation; Cholesterol supplementation may be achieved with SLOesterol instead of or in combination with egg yolk. SLOesterol is a powder formulation that contains cholesterol and natural emulsifier. It is considered a medical food developed by Solace Nutrition and available by prescription only.

Outcome Measures

Primary Outcome Measures :

1. To define the rate of progression of clinical and biochemical measures in patients with Smith Lemli-Opitz syndrome receiving dietary cholesterol supplementation. [ Time Frame: Once per year at annual study visit ]
   This study will measure changes in whole body cholesterol pool size, 24S, cholesterol absorption and synthesis in relation with cholesterol intake and changes in clincal end-points.

Secondary Outcome Measures :

1. Correlate biochemical and clinical phenotypes [ Time Frame: Once per year at annual study visit ]
   To correlate biochemical and clinical phenotypes in SLOS subjects given dietary cholesterol with changes in whole body cholesterol pool size, and with its major determinants (cholesterol synthesis, absorption and intake).
2. Identify clinical or biochemical markers for future therapeutic trials. [ Time Frame: Once per year at annual study visit ]
   To identify clinical or biochemical markers that can be used as outcome measures in a future therapeutic trial.
3. Identify a biochemical marker that can be used for diagnostic testing or screening. [ Time Frame: Once per year at annual study visit ]
   To identify a biochemical marker that can be used for diagnostic testing or screening
4. Develop a registry and repository of biomaterials of SLOS patients [ Time Frame: each subject will be enrolled in the registry at the baseline/initial visit, if they choose to participate in this portion of the study ]
   To develop a registry of well characterized SLOS patients and to maintain a repository of biomaterials corresponding to these patients

Eligibility Criteria

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Ages Eligible for Study:	up to 85 Years (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Confirmed diagnosis of Smith-Lemli-Opitz Syndrome (SLOS)
• Males and females of all ages
• Willing and able to travel to OHSU or another STAIR site

Exclusion Criteria:

• Subject does not have Smith-Lemli-Opitz Syndrome (SLOS)

Contacts and Locations

Locations

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United States, Maryland
Pdgen, Nichd, Nih, Dhhs
Bethesda, Maryland, United States, 20892
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, Ohio
Cincinnati Children'S Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children'S Hospital of Pittsburgh of Upmc
Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

Oregon Health and Science University

Investigators

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Principal Investigator:	Robert Steiner, MD	University of Wisconsin, Madison

More Information

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Responsible Party:	Jean-Baptiste Roullet, Clinical Professor, Oregon Health and Science University
ClinicalTrials.gov Identifier:	NCT01356420 History of Changes
Other Study ID Numbers:	STAIR 7001
First Posted:	May 19, 2011
Last Update Posted:	May 23, 2019
Last Verified:	May 2019

Keywords provided by Jean-Baptiste Roullet, Oregon Health and Science University:

SLOS

Additional relevant MeSH terms:

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Syndrome; Cleft Palate; Hypertelorism; Hypospadias; Genetic Diseases, X-Linked; Smith-Lemli-Opitz Syndrome; Disease; Pathologic Processes; Jaw Abnormalities; Jaw Diseases; Musculoskeletal Diseases; Maxillofacial Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Stomatognathic Diseases	Mouth Abnormalities; Mouth Diseases; Stomatognathic System Abnormalities; Congenital Abnormalities; Craniofacial Dysostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Penile Diseases; Genital Diseases, Male; Urogenital Abnormalities; Genetic Diseases, Inborn; Abnormalities, Multiple; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors