Fluid Biomarkers With Deep Phenotyping in Patients With ALS

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.

Endpoints for the study are:

- Motor unit number estimation will be performed on upper extremity muscles using the multipoint incremental technique (MIMUNE);

- Vital capacity, measured using slow vital capacity (SVC).

- Lower motor neuron excitability will be assessed with threshold tracking nerve conduction studies (ttNCS) in the least affected intrinsic hand muscle.

- Cognitive abnormalities will be assessed using the ALS Cognitive Behavior Screen (ALS-CBS);

- Upper motor neuron burden will be assessed using transcranial magnetic stimulation (TMS), employing a paired pulse protocol and recording from the least affected upper extremity intrinsic hand muscle;

- Hand held dynamometry (HHD) will be performed on 10 muscle groups tested bilaterally;

- Global function (ALSFRS-R); and

- Vital capacity, measured using slow vital capacity (SVC).

At each visit, blood will be collected and banked for biomarker discovery; CSF will be collected at baseline, month 6, and at month 18.

Other exploratory objectives of the study (to be performed at Barrow Neurological Institute only) will investigate to the composition of the "pellet" of processed CSF and a novel imaging marker called MRI cytography.

Study Locations Approximately 10 Northeast ALS Consortium (NEALS) Centers in the US will participate in the study. Sites that cannot perform the ttNCS and/or the TMS can still participate.

Number of Planned Subjects Fifty (50) subjects will be in the study. It is estimated that 5 subjects shall be enrolled per site.

Study Population This study will be conducted in subjects who meet the El Escorial criteria of possible, laboratory- supported probable, probable, or definite ALS. Time from diagnosis to study entry must be 24 months or less. At screening, eligible subjects must be at least 18 years old and must provide written informed consent. Detailed criteria will be described in the full protocol.

Duration of Study Active assessment period will be 18 months; a 1-year enrolment period is expected.