SOD1 Kinetics Measurements in ALS Patients
试验速览
- 阶段
- 不适用
- 状态
- 暂停
- 入组人数
- 86
- 试验地点
- 1
- 主要终点
- The primary outcome measurement will be the determination of the SOD1 half-life in the CSF of each subject.
研究概览
简要总结
Washington University in St. Louis is seeking participants with ALS for a study to determine the half-life of the protein SOD1 in the cerebral spinal fluid. Mutations in the SOD1 gene are known to cause some forms of familial ALS. Researchers are developing a treatment to reduce the level of SOD1 in familial ALS, but need to know more about how long SOD1 stays in the body ("half-life") to help determine if the new treatment is effective.
详细描述
Background: Novel targeted therapeutic strategies are being developed for genetic subsets of ALS, such as those caused by dominantly inherited mutations in the superoxide dismutase 1 gene (SOD1). Investigators have developed an antisense oligonucleotide (ASO) inhibitor of SOD1 biosynthesis for ALS patients who carry mutations in SOD1. This ASO is now ready for clinical trial (ClinicalTrials.gov #NCT02623699). The initial success of the ASO will depend on showing a pharmacodynamics result on SOD1 in participants, and thus a key challenge in applying this targeted therapy involves rigorous examination of pharmacodynamics markers.
The Investigator's previous data suggest that SOD1 in the cerebral spinal fluid (CSF) will be an excellent pharmacodynamics marker for an SOD1-focused therapeutic approach. However, one of the central missing components in understanding SOD1 as a marker is SOD1 CSF half-life data. The half-life of this protein will aid in clinical trial planning since half-life influences the amount of SOD1 protein reduction by ASO and thus dictates the optimal timing of drug administration and CSF collection for pharmacodynamics measures.
Objectives:
- Enroll a total of 86 ALS participants
- Determine the kinetics for total SOD1 protein, as well as the wild type and mutant protein separately
- Determine this in patients with known SOD1 mutation as well as sporadic ALS patients Eligibility
- Adults over age 18
- fALS with confirmed genetic testing showing a mutation in the SOD1 gene; asymptomatic SOD1 gene carriers and sporadic ALS patients.
Measures: The key outcome of this study is to determine the half-life of the SOD1 protein in symptomatic and asymptomatic ALS patients which will provide critical information to inform future therapeutic studies in ALS. For ALS patients, The Investigators will also perform Slow Vital Capacity testing and the ALSFRS-R at the screening visit and at each lumbar puncture visit.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 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
- 是
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
The primary outcome measurement will be the determination of the SOD1 half-life in the CSF of each subject.
时间窗: Assessed over 121 days
The half-life of total SOD1 protein will be determined in ALS patients using peptides that do not contain SOD1 mutation. The Investigators will analyze the kinetics of wild type SOD1 protein separately from mutant SOD1 protein using the mutation-containing peptide in order to determine differences in half-life using the stable isotope labeling kinetics (SILK) method of mass spectrometry.
次要结局
- ALS Functional Rating Scale-Revised (ALSFRS-R)(Baseline and weeks 1,2, 4, 9 and 17)
- Slow Vital Capacity (SVC)(Baseline and weeks 1,2, 4, 9 and 17)
研究者
Timothy M. Miller, MD, PhD
David Clayson Professor of Neurology
Washington University School of Medicine