Fluid Biomarkers With Deep Phenotyping in Patients With ALS
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 7
- 主要终点
- Multipoint incremental motor unit number estimates (MIMUNE)
研究概览
简要总结
This study aims to establish a biorepository and phenotyping database to investigate longitudinal changes in ALS subjects. Blood, including DNA and RNA, cerebrospinal fluid (CSF) and electrophysiologic measures will be collected every 6 months over 1 and a half years. The database and specimen repository will be made available to ALS researchers on a merit basis.
详细描述
Rationale for the Study
The Northeast ALS Consortium (NEALS) biorepository is an existing resource which has provided scientists with a wide range of samples associated with clinical information. It is primarily cross sectional in nature; longitudinal collections have been associated with a limited set of clinical and functional assessments. The investigators goal is to continue to build this repository with the collection protocol proposed here, to associate biofluid collection with specific measures of upper and lower motor neuron function. This project will compliment others to upgrade the NEALS biorepository infrastructure, including updating the computer systems, expanding the number of sample freezers and establishing a repository in the Western United States, and strengthening the standard operating procedures for the repository. The project also supports existing efforts to expand the biorepository by collecting new blood and spinal fluid samples from people with ALS.
Study Design This is a multicenter, non interventional, longitudinal study in patients with ALS. There will be four (4) subject visits in this study: Baseline, month 6, month 12, and month 18. At each visit, subjects will have biofluids collected, and be evaluated with assessment tools that focus on upper and lower motor neuron burden as well as cognitive function.
Study Objectives and Endpoints The primary objective of the study is to obtain deep phenotyping information on patients studied at regular intervals over 18 months, in conjunction with biofluid collection over that same time period.
The secondary objective of the study is to integrate data from this study to other ongoing projects via the NEALS biorepository, and future collections now being planned.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with sporadic ALS diagnosed as possible, laboratory-supported probable, probable or definite according to the World Federation of Neurology El Escorial criteria.
- •Expected to survive >1 year (12 months) after enrollment.
- •Male or female, aged 18-
- •Ability to medically undergo lumbar puncture (LP) as determined by the investigator (i.e., no bleeding disorder, allergy to local anesthetics, prior lumbar surgery which might make LP difficult, a skin infection at or near the LP site, or evidence of high intracranial pressure).
- •Willingness and medical ability to comply with scheduled visits, LP for CSF collection, laboratory tests, and other study procedures.
- •Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
- •Geographic accessibility to the study site.
排除标准
- •Any contraindications to having an LP, including but not limited to: Platelet count <100,000/µL.
- •History of bleeding disorder.
- •History of intolerance to the LP procedure.
- •Evidence of topical or other skin infection at the LP site.
- •History of allergy or other adverse reaction to local anesthetics used in the study.
- •History of traumatic central nervous system injury or stroke.
- •Other unspecified reasons that, in the opinion of the Investigator, make the subject unsuitable for enrollment.
- •Additional criteria for sites performing TMS:
- •Inability to perform either TMS or NCS studies due to insufficient motor evoked potential (MEP) or compound muscle action potential (CMAP) amplitude.
- •Contraindication to TMS studies including ferromagnetic metal in the head or neck (potentially found in aneurysm clips, implanted medication pumps, implanted brain stimulators, pacemakers, cochlear implants), or history of epilepsy. Dental fillings are permitted.
- •Additional criteria for sites performing MRI cytography:
- •Subjects who have a history of claustrophobia that cannot be adequately controlled.
- •Subjects who have a physical limitation related to fitting in the bore of the magnet.
- •Subjects who have a history of allergic reaction to contrast agents.
- •Subjects with a pacemaker, epicardia pacemaker wires, MRI-incompatible cardiac valve prostheses, MRI-incompatible vascular clips.
- •Subjects with MRI-incompatible cochlear implants.
- •Subjects with spinal nerve simulators.
- •Subjects with an infusion pump.
- •Subjects with metallic fragments in the eyes/orbits or in the vicinity of the brain or major neurovascular structures of the body, subjects with an employment history which involves exposure to welding, or subjects who have shrapnel any place in their body.
- •Subjects with acute kidney injury or renal insufficiency (eGFR of <20 ml/min/1.73 m^2) as they are at increased risk of Nephrogenic Systemic Fibrosis following administration of gadolinium-based MRI contrast agents.
- •Subjects unable to lay supine in the magnet because of orthopnea.
结局指标
主要结局
Multipoint incremental motor unit number estimates (MIMUNE)
时间窗: Every 6 months through month 18
MIMUNE is a validated technique to estimate the number of motor units in specific muscles of patients. In this study it will be performed on one intrinsic hand muscle unilaterally throughout the study.
Threshold tracking nerve conduction studies (ttNCS)
时间窗: Every 6 months through month 18
ttNCS is a technique that uses stimulation of peripheral motor nerves to measure a variety of variables to determine the excitability of the peripheral motor neurons.
ALS Functional Rating Scale Revised (ALSFRS-R)
时间窗: Every 6 months through month 18
The ALSFRS-R is a quickly administered (5 minutes) instrument used to determine subjects' assessment of their capability and independence in 12 functional activities, each rated on an ordinal scale (ratings 0-4).
Hand held dynamometry (HHD)
时间窗: Every 6 months through month 18
Hand held dynamometry (HHD) will be used as a quantitative measure of muscle strength for this study. 10 muscle groups will be examined bilaterally in both upper and lower extremities. Mean and standard deviation for each muscle group will be established from the initial values for each subject in this trial, so that strength determinations can be converted to Z scores and averaged to provide an HHD megascore for both upper and lower extremities.
Slow vital capacity (SVC)
时间窗: Every 6 months through month 18
Vital capacity will be measured as slow vital capacity (SVC) using standard technique
ALS cognitive behavioral screen (ALS-CBS)
时间窗: Every 6 months through month 18
The ALS Cognitive Behavioral Screen (ALS-CBS™) is a short measure of cognition and behavior in patients with Amyotrophic Lateral Sclerosis (ALS). The cognitive section includes commonly used elements of standard testing batteries, consisting of 8 tasks, with a possible total score of 20. It can be administered by a physician or other clinical care staff and takes approximately 5 minutes to complete. The behavioral section (ALS Caregiver Behavioral Questionnaire) is composed of questions sensitive to organic brain changes. It consists of a set of questions that compare changes in personality and behavior since the onset of ALS, as well as yes/no questions about mood, pseudobulbar affect, and fatigue. It is completed by a caregiver, family member or other informant during the same time that the patient completes the cognitive portion. The questionnaire typically takes about 2 minutes to complete.
Paired Pulse Stimulation Using Transcranial Magnetic Stimulation (TMS)
时间窗: Every 6 months through month 18
TMS is a technique that uses a focused magnetic field to depolarize neurons of interest. By depolarizing motor neurons and measuring the evoked response, an assessment of the neuronal excitability can be determined.
次要结局
未报告次要终点