Natural History Investigation Into Biochemical and Phenotypical Aspects of Smith-Lemli-Opitz Syndrome and Related Disorders of Cholesterol Metabolism
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 250
- 试验地点
- 1
- 主要终点
- The secondary objectives of these studies are to define comorbidities and mortality of the disease, to identify potential participants for future therapeutic trials and to evaluate possible laboratory outcome measures in carriers and suspected c...
研究概览
简要总结
Background:
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.
详细描述
Study Description: The objective of this study is to characterize the natural history of Smith-Lemli-Opitz Syndrome (SLOS) and related disorders (such as lathosterolosis, desmosterolosis, X-linked dominant chondrodysplasia punctata (CDPX2), CHILD syndrome, HEM dysplasia, and Antley-Bixler syndrome) by collecting both crosssectional and longitudinal data on individuals with these conditions.
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Day 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •INCLUSION CRITERIA:
- •Males or females of any age with any one of the following:
- •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.
排除标准
- •Affected individuals who cannot travel to the NIH because of their medical condition will be excluded from on-site participation. They may participate in the telemedicine or in the biomaterials parts of the study.
- •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.
研究组 & 干预措施
2
Subjects with Disorders of cholesterol synthesis and metabolism
1
Subjects with Smith-Lemli-Opitz syndrome
结局指标
主要结局
The secondary objectives of these studies are to define comorbidities and mortality of the disease, to identify potential participants for future therapeutic trials and to evaluate possible laboratory outcome measures in carriers and suspected c...
时间窗: ongoing
To describe in more detail long term manifestations of SLOS and disorders of cholesterol synthesis.
The primary objective of this study is to determine laboratory or clinical outcome measures that could be used in future therapeutic trials.
时间窗: ongoing
We will obtain data from patient evaluations that may be used as therapeutic targets in the fututre.
次要结局
未报告次要终点