Amyotrophic Lateral SclerosisNCT02611674
Methodology Study of Novel Outcome Measures to Assess Progression of ALS
An observational study of Amyotrophic Lateral Sclerosis, run by Biogen at 21 sites in 9 countries.
Trial summary
The primary objectives of the study are to estimate and rank-order the longitudinal standardized mean changes over 6 months and over 12 months, for a set of outcome measures administered to participants with amyotrophic lateral sclerosis (ALS), in order to identify measures that are more sensitive to disease… Read more about this study
- Who is it for?
- Ages 16 to 85 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- How many people
- 138 participants
- Where
- 21 sitesin 9 countries
- Study dates
- 6 Jan 2016to 1 Aug 2019
- 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 16 to 85 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Participants suffering from ALS are recruited by participating physicians in a standard clinical practice setting.
Who may be able to join
- A diagnosis of sporadic or familial ALS
- ALS onset within ≤5 years
- Must be 16 to 85 years of age, inclusive, for sites in the United States and 18 to 85 years of age, inclusive, for all sites outside of the United States
Who cannot join
- History of or positive test result at Screening for human immunodeficiency virus (HIV)
- History of or positive test result at Screening for hepatitis C virus (HCV) antibody or hepatitis B virus (HBV)
- Possibility of neuromuscular weakness other than ALS
- Unspecified reasons that, in the opinion of the site Investigator, make the subject unsuitable for enrollment or unlikely to be able to complete, at a minimum, the Month 6 Visit
- NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply
Trial locations and contacts
21 sites in 9 countries.
21 sites in 9 countries
United States8 sites
The Emory Clinic
Atlanta, Georgia, 30322
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Massachusetts General Hospital, MA
Charlestown, Massachusetts, 2129
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, EC037
University of California San Diego Medical Center
San Diego, California, 92103
California Pacific Medical Center
San Francisco, California, 94115
Washington University School of Medicine
St Louis, Missouri, 63110
University of South Florida
Tampa, Florida, 33612
Germany4 sites
Charite - Campus Virchow-Klinikum
Berlin, 13125
Medizinische Hochschule Hannover
Hanover, 30625
Universitaetsklinikum Jena
Jena, 07743
Universitaetsklinikum Ulm
Ulm, 89081
Canada2 sites
Montreal Neurological Institute Clinical Research Unit
Montreal, Quebec, H3A 2B4
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
France2 sites
Hopital Gui de Chauliac, Service de Neurologie
Montpellier, Hérault, 34295
Groupe Hospitalier Pitie-Salpetriere
Paris, Paris, 75013
United Kingdom1 site
Royal Hallamshire Hospital
Sheffield, West Midlands, S102JF
About this study
Official title: Methodology Study of Novel Electrophysiological, Physical, and Imaging Outcome Measures to Assess the Progression of Amyotrophic Lateral Sclerosis
The primary objectives of the study are to estimate and rank-order the longitudinal standardized mean changes over 6 months and over 12 months, for a set of outcome measures administered to participants with amyotrophic lateral sclerosis (ALS), in order to identify measures that are more sensitive to disease progression than Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). The secondary objectives of this study are: To evaluate the test-retest reproducibility of each outcome measure; To determine correlations between 6 and 12-month changes in all exploratory measures with 18 and 24-month changes in ALSFRS-R and survival; To assess correlations between/among the various measures; To obtain biological samples in order to identify molecular correlates to the clinical measures and to further characterize previously identified and novel molecular biomarkers of disease progression for incorporation into future clinical studies.
- Conditions
- Amyotrophic Lateral Sclerosis
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What is being measured
The primary outcome is the main question the study is designed to answer.
Longitudinal standardized mean change in electrophysiological measures as assessed by electrical impedance myography (EIM)
EIM is an electrophysiological technique in which current is applied to a muscle of interest and resultant voltage and impedance are measured. These measured parameters reflect the conductivity of underlying tissue and presumably the pathologic state of denervated muscle in an ALS participant
Measured: Baseline to Month 6 and Baseline to Month 12
Longitudinal standardized mean change in electrophysiological measures as assessed by compound muscle action potential (CMAP)
CMAP is a standard electrophysiological measure generated by maximally stimulating a nerve such that all muscle fibers innervated by the respective nerve are depolarized. Reduction of CMAP amplitude reflects loss of motor axons and, therefore, is directly relevant to ALS.
Measured: Baseline to Month 6 and Baseline to Month 12
Longitudinal standardized mean change in electrophysiological measures as assessed by motor unit number estimation (MUNE)
Optional, to be administered at each site's Investigator's discretion. MUNE is used to estimate the number of functioning motor units.
Measured: Baseline to Month 6 and Baseline to Month 12
Longitudinal standardized mean change in electrophysiological measures as assessed by motor unit number index (MUNIX)
MUNIX estimates functioning motor units within a muscle. CMAP and surface electromyography potentials (surface interference patterns) are obtained at various levels of voluntary effort, and MUNIX is estimated using power and area of CMAP and surface interference patterns.
Measured: Baseline to Month 6 and Baseline to Month 12
Longitudinal standardized mean change in muscle strength measures as assessed by hand-held dynamometry (HHD)
HHD tests isometric strength of multiple muscles using standard participant positioning. Approximately 10 muscle groups will be examined (per each side) in both upper and lower extremities.
Measured: Baseline to Month 6 and Baseline to Month 12
Longitudinal standardized mean change in respiratory measures as assessed by slow vital capacity (SVC)
Vital capacity will be measured by means of an SVC test, administered in the upright position. Upright SVC will be determined by performing 3 to 5 measures, in accordance with criteria established by the American Thoracic Society and the European Respiratory Society.
Measured: Baseline to Month 6 and Baseline to Month 12
Longitudinal standardized mean change in functional measures as assessed by Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
The ALSFRS-R has been demonstrated to predict survival. The ALSFRS-R measures 4 functional domains, including respiratory, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48 [Cedarbaum 1999], with higher scores representing better function.
Measured: Baseline to Month 6 and Baseline to Month 12
Secondary outcomes (12)
Within-participant test-retest reliability between the 2 repeated measurements occurring on Day 1 and Day 7 for EIM
Measured: Day 1 and Day 7
Within-participant test-retest reliability between the 2 repeated measurements for CMAP
Measured: Day 1 and Day 7
Within-participant test-retest reliability between the 2 repeated measurements for MUNE
Measured: Day 1 and Day 7
Within-participant test-retest reliability between the 2 repeated measurements for MUNIX
Measured: Day 1 and Day 7
Within-participant test-retest reliability between the 2 repeated measurements for HHD
Measured: Day 1 and Day 7
Within-participant test-retest reliability between the 2 repeated measurements for SVC
Measured: Day 1 and Day 7
Within-participant test-retest reliability between the 2 repeated measurements for ALSFRS-R
Measured: Day 1 and Day 7
Comparison between 6 and 12-month changes in exploratory measures with 18 and 24-month changes in ALSFRS-R and survival
Measured: Baseline to Month 24
Comparison between 6-month changes for muscle electrophysiological measures
Measured: Baseline to Month 12
Comparison between 6-month changes for muscle strength measures
Measured: Baseline to Month 12
Comparison between 6-month changes for functional measures
Measured: Baseline to Month 12
Comparison of molecular biomarkers with disease progression
Measured: Baseline to Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2015 (estimated)
- Study start6 Jan 2016
- Primary completion27 Jul 2018
- Study completion1 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 138 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02611674
- Sponsor's protocol ID
- 999AS003
- Status last verified
- Oct 2019
- First submitted
- 8 Oct 2015
- Last updated
- 24 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Methodology Study of Novel Electrophysiological, Physical, and Imaging Outcome Measures to Assess the Progression of Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT02611674
- Acronym / sponsor ID
- 999AS003
- Conditions
- Amyotrophic Lateral Sclerosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 138 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 6 Jan 2016 (actual)
- Primary completion
- 27 Jul 2018 (actual)
- Study completion
- 1 Aug 2019 (actual)
- First posted
- 23 Nov 2015 (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.
The primary objectives of the study are to estimate and rank-order the longitudinal standardized mean changes over 6 months and over 12 months, for a set of outcome measures administered to participants with amyotrophic lateral sclerosis (ALS), in order to identify measures that are more sensitive to disease progression than Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). The secondary objectives of this study are: To evaluate the test-retest reproducibility of each outcome measure; To determine correlations between 6 and 12-month changes in all exploratory measures with 18 and 24-month changes in ALSFRS-R and survival; To assess correlations between/among the various measures; To obtain biological samples in order to identify molecular correlates to the clinical measures and to further characterize previously identified and novel molecular biomarkers of disease progression for incorporation into future clinical studies.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 16 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Participants suffering from ALS are recruited by participating physicians in a standard clinical practice setting.
Key inclusion criteria (3 listed)
- A diagnosis of sporadic or familial ALS
- ALS onset within ≤5 years
- Must be 16 to 85 years of age, inclusive, for sites in the United States and 18 to 85 years of age, inclusive, for all sites outside of the United States
Key exclusion criteria (5 listed)
- History of or positive test result at Screening for human immunodeficiency virus (HIV)
- History of or positive test result at Screening for hepatitis C virus (HCV) antibody or hepatitis B virus (HBV)
- Possibility of neuromuscular weakness other than ALS
- Unspecified reasons that, in the opinion of the site Investigator, make the subject unsuitable for enrollment or unlikely to be able to complete, at a minimum, the Month 6 Visit
- NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply
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
Longitudinal standardized mean change in electrophysiological measures as assessed by electrical impedance myography (EIM)
Time frame: Baseline to Month 6 and Baseline to Month 12
EIM is an electrophysiological technique in which current is applied to a muscle of interest and resultant voltage and impedance are measured. These measured parameters reflect the conductivity of underlying tissue and presumably the pathologic state of denervated muscle in an ALS participant
Longitudinal standardized mean change in electrophysiological measures as assessed by compound muscle action potential (CMAP)
Time frame: Baseline to Month 6 and Baseline to Month 12
CMAP is a standard electrophysiological measure generated by maximally stimulating a nerve such that all muscle fibers innervated by the respective nerve are depolarized. Reduction of CMAP amplitude reflects loss of motor axons and, therefore, is directly relevant to ALS.
Longitudinal standardized mean change in electrophysiological measures as assessed by motor unit number estimation (MUNE)
Time frame: Baseline to Month 6 and Baseline to Month 12
Optional, to be administered at each site's Investigator's discretion. MUNE is used to estimate the number of functioning motor units.
Longitudinal standardized mean change in electrophysiological measures as assessed by motor unit number index (MUNIX)
Time frame: Baseline to Month 6 and Baseline to Month 12
MUNIX estimates functioning motor units within a muscle. CMAP and surface electromyography potentials (surface interference patterns) are obtained at various levels of voluntary effort, and MUNIX is estimated using power and area of CMAP and surface interference patterns.
Longitudinal standardized mean change in muscle strength measures as assessed by hand-held dynamometry (HHD)
Time frame: Baseline to Month 6 and Baseline to Month 12
HHD tests isometric strength of multiple muscles using standard participant positioning. Approximately 10 muscle groups will be examined (per each side) in both upper and lower extremities.
Longitudinal standardized mean change in respiratory measures as assessed by slow vital capacity (SVC)
Time frame: Baseline to Month 6 and Baseline to Month 12
Vital capacity will be measured by means of an SVC test, administered in the upright position. Upright SVC will be determined by performing 3 to 5 measures, in accordance with criteria established by the American Thoracic Society and the European Respiratory Society.
Longitudinal standardized mean change in functional measures as assessed by Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
Time frame: Baseline to Month 6 and Baseline to Month 12
The ALSFRS-R has been demonstrated to predict survival. The ALSFRS-R measures 4 functional domains, including respiratory, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48 [Cedarbaum 1999], with higher scores representing better function.
12 secondary outcomes
Within-participant test-retest reliability between the 2 repeated measurements occurring on Day 1 and Day 7 for EIM
Time frame: Day 1 and Day 7
Within-participant test-retest reliability between the 2 repeated measurements for CMAP
Time frame: Day 1 and Day 7
Within-participant test-retest reliability between the 2 repeated measurements for MUNE
Time frame: Day 1 and Day 7
Within-participant test-retest reliability between the 2 repeated measurements for MUNIX
Time frame: Day 1 and Day 7
Within-participant test-retest reliability between the 2 repeated measurements for HHD
Time frame: Day 1 and Day 7
Within-participant test-retest reliability between the 2 repeated measurements for SVC
Time frame: Day 1 and Day 7
Within-participant test-retest reliability between the 2 repeated measurements for ALSFRS-R
Time frame: Day 1 and Day 7
Comparison between 6 and 12-month changes in exploratory measures with 18 and 24-month changes in ALSFRS-R and survival
Time frame: Baseline to Month 24
Comparison between 6-month changes for muscle electrophysiological measures
Time frame: Baseline to Month 12
Comparison between 6-month changes for muscle strength measures
Time frame: Baseline to Month 12
Comparison between 6-month changes for functional measures
Time frame: Baseline to Month 12
Comparison of molecular biomarkers with disease progression
Time frame: Baseline to Month 12
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 24 Oct 2019.
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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.
Medical Director study director
Biogen
21 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Amyotrophic Lateral Sclerosis, run by Biogen at 21 sites in 9 countries.
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 3 inclusion and 5 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 24 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Germany, Canada, France, Belgium and 4 more countries. 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?
Longitudinal standardized mean change in electrophysiological measures as assessed by electrical impedance myography (EIM) (time frame: Baseline to Month 6 and Baseline to Month 12). 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 24 Oct 2019.