Deep Phenotyping in Patients With ALS

NCT02819765 | Completed

• 2 other identifiers: ALSA-BIO3PHX16BN016
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

ALS; Motor Neuron Disease

Outcome Measures

Primary Outcomes (7)

• ALS Functional Rating Scale Revised (ALSFRS-R)

  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).

  Every 6 months through month 18

• Slow vital capacity (SVC)

  Vital capacity will be measured as slow vital capacity (SVC) using standard technique

  Every 6 months through month 18

• Hand held dynamometry (HHD)

  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.

  Every 6 months through month 18

• ALS cognitive behavioral screen (ALS-CBS)

  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.

  Every 6 months through month 18

• Multipoint incremental motor unit number estimates (MIMUNE)

  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.

  Every 6 months through month 18

• Paired Pulse Stimulation Using Transcranial Magnetic Stimulation (TMS)

  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.

  Every 6 months through month 18

• Threshold tracking nerve conduction studies (ttNCS)

  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.

  Every 6 months through month 18

Other Outcomes (1)

• MRI Cytography

  At baseline and at 6 months

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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 18-75.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Barrow Neurological Institute: lead
• ALS Association: collaborator

Study Sites (7)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

Hospital for Special Surgery (HSS)

New York, New York, 10021, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Temple University

Philadelphia, Pennsylvania, 19122, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Department of Neurosurgery & Neurology | Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood Serum Cerebrospinal fluid RNA DNA

MeSH Terms

Conditions

Motor Neuron Disease

Condition Hierarchy (Ancestors)

Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases

Study Officials

• Shafeeq Ladha, MD

  Barrow Neurological Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2016
• First Posted: June 30, 2016
• Study Start: February 7, 2017
• Primary Completion: November 9, 2021
• Study Completion: November 9, 2021
• Last Updated: December 16, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share

Locations

US (7)