Longitudinal Study of Innate Lymphoid Cells in Peripheral Blood in ALS
研究概览
详细说明
Application - HUM00107546
Study Title:
Longitudinal Study of Innate Lymphoid Cells in Peripheral Blood in ALS
Full Study Title:
Longitudinal Study of Innate Lymphoid Cells in Peripheral Blood in ALS
If there are other U-M studies related to this project, enter the eResearch ID number (HUM#) or IRBMED Legacy study number. Examples of related projects include, but are not limited to:
00028826 - Epidemological Risk Factors and The Genetics of ALS
Principal Investigator:
- Benjamin Murdock, PhD
Study Team Members:
- Eva Feldman, MD, PhD Co-Investigator
- Stephen Goutman, MD Co-Investigator
- Claudia Figueroa-Romero, Research Investigator
- Crystal Pacut, Biorepository Coordinator
- Jayna Duell, Study Coordinator
- Blake Swihart, Study Coordinator
- Adam Patterson, Biostatistician
Project Summary:
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by progressive muscle weakness and eventual death. Studies demonstrate that the immune system plays a key role in ALS progression; however, the role of the immune system is unclear, as various aspects can play both a beneficial and detrimental role in the disease course. Attempts to universally suppress the immune system in ALS patients have at best had negligible effects on progression or at worst accelerated the disease. Alternatively, augmenting or depleting specific immune cell populations in ALS mouse models alters the disease course and slows progression. Thus, there is a critical need to identify immune cell populations to serve as biomarkers and therapeutic targets.
Neuroinflammation is a hallmark of ALS in both human patients and mouse models. While clinical symptoms result from motor neuron degeneration, it is becoming increasingly clear that the immune system plays a key role in pathology. A variety of insults give rise to identical immune responses which go on to produce the characteristic clinical and histopathological manifestations of motor neuron disease. This makes the immune system an attractive target for therapeutics, as the wide variety of potential ALS sources all funnel through a common immunological pathway over the course of disease. The investigators recent studies have demonstrated that ALS patients have increased levels of several subpopulations of innate lymphoid cells (ILCs) in their peripheral blood. A subset of patients has ILC levels 5-10 times greater than those found in healthy control patients. The differences seen in the ILC levels in peripheral blood are much greater differences seen in other immune cell populations during ALS. Thus, these cell populations are attractive candidates for use as biomarkers or therapeutic targets.
The proposed study can be broken into three broad phases which will applicable to each patient: recruitment, sample collection, and analysis. Following diagnosis of disease, ALS patients who live within 1 hour of the University of Michigan will be called by our clinical coordinator and enrolled in the study (recruitment). Following enrollment in the study, each of the patients will be visited once every 28 ± 5 days for a year after the initial visit by a Michigan Institute for Clinical & Health Research (MICHR) clinical research unit; this unit will take 20 ml of blood per patient. Samples will then be returned to the University of Michigan. ILCs will be isolated from peripheral blood using fluorescence-activated cell sorting (FACS) and the mRNA of each ILC population will be collected and cytokine production analyzed using multiplex (analysis). On the day of collection, a clinician or clinical coordinator from the University of Michigan Comprehensive ALS Clinic (UMCAC) will contact the patient to complete an ALSFRS-R questionnaire to assess the physical deterioration of the patients.
The study will also incorporate control subjects. The control subjects will have blood taken once a month for 12 total visits over 36 months, but will not complete the ALSFRS-R questionnaire as they will not have been diagnosed with ALS and therefore the questionnaire does not fit; 20ml of blood will be taken per visit.
Subjects need to live within approximately 60 miles of the University of Michigan.
研究类型
注册 (实际的)
联系人和位置
学习地点
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Michigan
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Ann Arbor、Michigan、美国、48109
- University of Michigan
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
Inclusion Criteria:
- Age 18 years or older.
- Clinically definite, probable, probable laboratory supported, or possible ALS by El Escorial criteria
- Fluency in English at the 6th grade level or higher.
- Able to communicate sufficiently well by speaking
- Able to communicate over the phone.
- Capable of providing informed consent.
- Lives geographically accessible to the University of Michigan
Exclusion Criteria:
- Unable to provide informed consent.
- Clinically significant dementia, as judged by the site investigator.
- Other neurological or psychiatric disorders which are expected to impair cognitive function.
- Other serious and uncontrolled medical disorders.
- History of autoimmune disease.
- Use of prednisone, IVIG, or immunosuppression within the last 12 months.
- Not geographically accessible to the University of Michigan
学习计划
研究是如何设计的?
设计细节
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Total number of classical NK (natural killer) cells; total number of CD3+ CD4+ CD8+ cells
大体时间:Every 28 days (+/- 5 days) for 12 total visits over 36 months
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Total number of classical NK cells; total number of CD3+ CD4+ CD8+ cells
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Every 28 days (+/- 5 days) for 12 total visits over 36 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Cytokine expression
大体时间:Every 28 days (+/- 5 days) for 12 total visits over 36 months
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Cytokine expression levels of these cell populations using qPCR, RNA-Seq, or Luminex.
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Every 28 days (+/- 5 days) for 12 total visits over 36 months
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合作者和调查者
调查人员
- 首席研究员:Ben Murdock, PhD、University of Michigan
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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