Deep Phenotyping in Patients With ALS
Condition: ALS; Motor Neuron Disease
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        ALS patient volunteers will be invited to participate in this study by their neurologists
        either in clinic or at a regular scheduled appointment visit.
      
Biospecimen description: 
      Blood Serum Cerebrospinal fluid RNA DNA