ALSNCT02819765
Deep Phenotyping in Patients With ALS
An observational study of ALS and Motor Neuron Disease, run by Barrow Neurological Institute at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- ALS, Motor Neuron Disease
- How many people
- 32 participants
- Where
- 7 sitesUnited States
- Study dates
- 7 Feb 2017to 9 Nov 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 21Show fewer
- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Department of Neurosurgery & Neurology | Medical University of South Carolina
Charleston, South Carolina, 29425
Spectrum Health
Grand Rapids, Michigan, 49503
Hospital for Special Surgery (HSS)
New York, New York, 10021
Temple University
Philadelphia, Pennsylvania, 19122
Barrow Neurological Institute
Phoenix, Arizona, 85013
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Oregon Health & Science University
Portland, Oregon, 97239
About this study
Official title: Fluid Biomarkers With Deep Phenotyping in Patients With ALS
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.
Read the 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.
- Conditions
- ALS, Motor Neuron Disease
- Medical subject headings
- Motor Neuron Disease
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Every 6 months through month 18
Slow vital capacity (SVC)
Vital capacity will be measured as slow vital capacity (SVC) using standard technique
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Every 6 months through month 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2016 (estimated)
- Study start7 Feb 2017
- Primary completion9 Nov 2021
- Study completion9 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ALSStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barrow Neurological Institute
- Sponsor type
- University, hospital or other
- Collaborators
- ALS Association
- Responsible party
- Sponsor
- Investigators
- Shafeeq Ladha, MD, Principal investigator, Barrow Neurological Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02819765
- Sponsor's protocol ID
- ALSA-BIO3
- Other IDs
- PHX16BN016
- Status last verified
- Dec 2021
- First submitted
- 7 Jun 2016
- Last updated
- 16 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data will be part of the Northeast ALS consortium biorepository database.
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fluid Biomarkers With Deep Phenotyping in Patients With ALS
- ClinicalTrials.gov ID
- NCT02819765
- Acronym / sponsor ID
- ALSA-BIO3
- Conditions
- ALS, Motor Neuron Disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Barrow Neurological InstituteUniversity, hospital or other
- Collaborators
- ALS Association
- Study start
- 7 Feb 2017 (actual)
- Primary completion
- 9 Nov 2021 (actual)
- Study completion
- 9 Nov 2021 (actual)
- First posted
- 30 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
ALS Functional Rating Scale Revised (ALSFRS-R)
Time frame: 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).
Slow vital capacity (SVC)
Time frame: Every 6 months through month 18
Vital capacity will be measured as slow vital capacity (SVC) using standard technique
Hand held dynamometry (HHD)
Time frame: 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.
ALS cognitive behavioral screen (ALS-CBS)
Time frame: 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.
Multipoint incremental motor unit number estimates (MIMUNE)
Time frame: 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.
Paired Pulse Stimulation Using Transcranial Magnetic Stimulation (TMS)
Time frame: 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.
Threshold tracking nerve conduction studies (ttNCS)
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2021.
- Individual participant dataSharing planned: Yes. The data will be part of the Northeast ALS consortium biorepository database.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shafeeq Ladha, MD principal investigator
Barrow Neurological Institute
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of ALS and Motor Neuron Disease, run by Barrow Neurological Institute at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ALS Functional Rating Scale Revised (ALSFRS-R) (time frame: Every 6 months through month 18). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2021.