Clinical trial NCT01356420: Sterol and Isoprenoid Disease Research Consortium: Smith-Lemli-Opitz Syndrome
Official title: Smith-Lemli-Opitz Syndrome: A Longitudinal Clinical Study of Patients Receiving Cholesterol Supplementation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Smith-Lemli-Opitz Syndrome
Keywords: SLOS
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
First posted: 2011-05-19
Enrollment: 21
Sex: ALL
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Eligibility 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)

Primary outcomes:
measure: To define the rate of progression of clinical and biochemical measures in patients with Smith Lemli-Opitz syndrome receiving dietary cholesterol supplementation.
timeFrame: Once per year at annual study visit
Secondary outcomes:
measure: Correlate biochemical and clinical phenotypes
timeFrame: Once per year at annual study visit
measure: Identify clinical or biochemical markers for future therapeutic trials.
timeFrame: Once per year at annual study visit
measure: Identify a biochemical marker that can be used for diagnostic testing or screening.
timeFrame: Once per year at annual study visit
measure: Develop a registry and repository of biomaterials of SLOS patients
timeFrame: each subject will be enrolled in the registry at the baseline/initial visit, if they choose to participate in this portion of the study
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Pdgen, Nichd, Nih, Dhhs
state: Maryland
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Cincinnati
country: United States
facility: Cincinnati Children'S Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Pittsburgh
country: United States
facility: Children'S Hospital of Pittsburgh of Upmc
state: Pennsylvania
Study officials:
affiliation: University of Wisconsin, Madison
name: Robert Steiner, MD
role: PRINCIPAL_INVESTIGATOR
References: