Integrating Genetic and Environmental Risk Scores Into an Algorithm to Predict Multiple Sclerosis Susceptibility
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 181
- 试验地点
- 1
- 主要终点
- presence or absence of lesions on T2-weighted brain MRI
研究概览
简要总结
Background:
- Research shows that both genes and the environment influence a person s risk for getting multiple sclerosis (MS). However, it is not possible to accurately predict who will develop MS. Researchers want to study people with MS and their family members. They have developed a Genetic and Environmental Risk Score for MS. This score combines information from a person's medical history and genes. It also includes environmental factors that may be related to developing MS. This study will test this risk score to see if it can help predict who will develop MS.
Objectives:
- To evaluate a score for genetic and environmental risk factors that may help predict whether a person will develop MS.
Eligibility:
- Individuals at least 18 years of age who have MS.
- Individuals between 18 to 50 years of age who are the parent, brother, sister, or child of a person with MS.
Design:
- People with MS will allow researchers to look at their personal and medical data. These data will have been collected in other MS-related studies.
- Relatives of people with MS will fill out a questionnaire and give blood and saliva samples. They will fill out the questionnaire again one year later.
- Some relatives will have additional optional testing. These tests will include a physical exam and imaging studies. There may also be other tests. These tests may be repeated every 1 to 5 years for 20 years.
详细描述
Objective. The overall objective of this study is to investigate the genetic, immune, and neuroimaging profiles that may increase a person s risk of developing multiple sclerosis (MS) in order to identify and validate predictive biomarkers in populations at risk for this disorder.
Study population. There will be three study populations:
-
Individuals at risk for developing MS As part of the Genes and Environment in Multiple Sclerosis (GEMS) study, we plan to recruit up to 1000 first-degree relatives of MS patients. GEMS is a study aiming to recruit 5000 individuals that is being led by our collaborators at Columbia University Medical Center. For the purposes of this study, a first-degree relative may be a parent, sibling, or child between 18 and 50 years of age but must not carry a diagnosis of MS. The first-degree relative must have the ability to provide consent and be willing to participate in the study. Two potentially overlapping subsets of these individuals will undergo detailed testing at the NIH:
-
The cross-sectional subcohort will consist of up to 150 participants with combined genetic and environmental risk scores (GERS), defined in the protocol, in the highest and lowest 20 percent of the entire study population. Selected participants may be invited for follow-up studies based on data obtained at baseline if symptoms develop.
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The NINDS longitudinal subcohort will consist of up to 10 participants, ages 18 to 40,who express willingness to be followed for 20 years at the NIH, whose GERS falls in the top 20 percent of the entire study population, and who have a first-degree relative with MS who is participatipate
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MS patients - We plan to recruit up to 1000 MS patients whose first-degree relatives are enrolled this study. These participants either: (A) will be evaluated under other Neuroimmunology Branch Clinic protocols and will not undergo separate evaluation under this protocol; or (B) will send us medical records confirming their MS diagnosis via mail/fax/secure email, without the requirement to participate in another NIH protocol. The purpose of including this cohort in the current study is to allow access to their clinical, biological, and imaging data for comparison with first-degree relatives, if available, and to confirm that existing GEMS participants have a first-degree relative diagnosed with MS.
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Healthy volunteers - We plan to recruit up to 80 healthy volunteers, ages 18-50, who do not have a known first-degree relative with MS. The purpose of including this cohort in the current study is to allow quantification of the degree and extent of abnormalities, including abnormalities of the blood-brain barrier, in individuals at risk for developing MS. Without imaging data obtained from healthy volunteers, there is no way to determine whether subtle clinical and neuroimaging findings in the at-risk cohort are truly abnormal, or to correctly threshold and quantify the observed abnormalities.
Design. This is a prospective cohort natural-history study. All GEMS participants will complete the following study procedures, which can be performed offsite: informed consent; study questionnaire; saliva sample; and blood draw. The questionnaire will be repeated 1 year after enrollment.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •GEMS cohort (target n equals 1000)
- •First-degree relative (parent, sibling, or child) of a self-reported MS patient.
- •Age 18-50, inclusive, at the time of enrollment into the overall GEMS study.
- •Willingness to be contacted regarding additional follow-up procedures.
- •Cross-sectional subcohort (target n equal 150):
- •Referred by Columbia University Medical Center as having a genetic and environmental risk score (GERS), defined in Section 4.1.1, in the top or bottom 20% of the overall GEMS study.
- •NINDS Longitudinal subcohort (target n equal 100):
- •Ages 18-40, inclusive.
- •Referred by Columbia University Medical Center as having a GERS in the top 20% of the overall GEMS study.
- •Willing to undergo additional study procedures at the NIH for up to 20 years, with planned follow-up every year for participants between ages 18 and 25, every 2 years for participants between ages 26 and 30, and every 5 years for participants between ages 31 and
- •Relative enrolled in NIH study with confirmation of MS diagnosis.
- •MS patient cohort (target n=1000):
- •MS patients (NIH)
- •Co-enrolled in another Neuroimmunology Clinic natural history protocol.
- •Diagnosis confirmed at NIH.
- •Age 18 or older.
- •MS patient (non-NIH)
- •First-degree relative (parent, sibling, or child) of an existing GEMS participant.
- •Able and willing to send medical records associated with their MS diagnosis to NIH.
- •Healthy volunteer cohort (target n=80)
- •Age 18-50, inclusive.
- •No known first-degree relative (parent, sibling, or child) with MS.
- •All cohorts
- •Able to give informed consent.
排除标准
- •GEMS cohort
- •Diagnosis of MS.
- •Cross-sectional and NINDS longitudinal subcohorts
- •Contraindications to MRI scanning.
- •Diagnosis of another central nervous system disease disease (CNS neoplasm, known cerebrovascular disease, known CNS degenerative diseases, or known CNS inflammatory diseases) at the time enrollment into the study.
- •MS cohort (both)
- •Healthy volunteer cohort
- •Diagnosis of MS or another central nervous system (CNS neoplasm, cerebrovascular disease CNS degenerative diseases, or CNS inflammatory diseases) or a systemic disease that would interfere with the aims of this study.
- •Contraindications to MRI scanning.
- •Eligible NIH employees and staff may participate.
研究组 & 干预措施
GEMS cohort
Individuals at risk for developing MS
Healthy volunteer cohort
healthy volunteers, ages 18-50, who do not have a known first-degree relative with MS
MS patient cohort
MS patients whose first-degree relatives are enrolled in this study
结局指标
主要结局
presence or absence of lesions on T2-weighted brain MRI
时间窗: ongoing
For participants in the cross-sectional cohort, which consists of individuals at highest and lowest risk for MS, the primary outcome measure is the presence or absence of lesions on T2-weighted brain MRI that meet the 2010 MRI criteria for dissemination in space.
GERS
时间窗: ongoing
For participants in the overall GEMS study, the primary outcome measure is the GERS itself, as most participants in this cohort will not undergo further testing.
次要结局
- development of MS-like abnormalities on brain imaging studies, abnormalities on laboratory testing, and clinical symptoms and signs.(ongoing)
- The time lag between defined exposures(ongoing)
- The time lag between the appearance of asymptomatic radiological and laboratory abnormalities and the onset of clinical symptoms;(ongoing)
- exploratory clinical, imaging, biological data in the cross sectional(ongoing)