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Methodology Study of Novel Outcome Measures to Assess Progression of ALS

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02611674
First Posted: November 23, 2015
Last Update Posted: September 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Biogen
October 8, 2015
November 23, 2015
September 4, 2017
January 6, 2016
May 7, 2018   (Final data collection date for 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 ]
    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.
  • 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 muscle strength measures as assessed by Tongue strength, measured with the Iowa Oral Performance Instrument (IOPI) [ Time Frame: Baseline to Month 6 and Baseline to Month 12 ]
    The IOPI is a commercially available tongue pressure measurement system composed of an air-filled bulb connected to a pressure transducer. The bulb can be placed in different positions in the mouth in order to assess different aspects of tongue weakness.
  • Longitudinal standardized mean change in respiratory measures as assessed by sniff nasal inspiratory pressure (SNIP) [ Time Frame: Baseline to Month 6 and Baseline to Month 12 ]
    SNIP is a test of inspiratory force (sternocleidomastoid and diaphragm) that is measured from a nasal cannula.
  • 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 respiratory measures as assessed by forced expiratory volume in 6 seconds (FEV6) [ Time Frame: Baseline to Month 6 and Baseline to Month 12 ]
    FEV6 is the volume of air that can be blown out in 6 seconds following full inspiration.
  • Longitudinal standardized mean change in functional measures as assessed by Center for Neurologic Study - bulbar function scale (CNS-BFS) [ Time Frame: Baseline to Month 6 and Baseline to Month 12 ]
    The CNS-BFS is a self-report scale designed for the assessment of bulbar function in ALS. The CNS-BFS consists of 21 questions that are designed to sensitively assess salivation, speech, and swallowing.
  • 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.
Complete list of historical versions of study NCT02611674 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 IOPI [ Time Frame: Day 1 and Day 7 ]
  • Within-participant test-retest reliability between the 2 repeated measurements for SNIP [ 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 FEV6 [ Time Frame: Day 1 and Day 7 ]
  • Within-participant test-retest reliability between the 2 repeated measurements for CNS-BFS [ 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 ]
  • Standardized mean change over 6 months of the ALSFRS-R (bulbar domain) versus CNS-BFS in participants with bulbar involvement [ Time Frame: Baseline to Month 12 ]
  • Comparison of molecular biomarkers with disease progression [ Time Frame: Baseline to Month 12 ]
Not Provided
Not Provided
 
Methodology Study of Novel Outcome Measures to Assess Progression of ALS
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 novel 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.
Not Provided
Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Not Provided
Probability Sample
Participants suffering from ALS are recruited by participating physicians in a standard clinical practice setting.
Amyotrophic Lateral Sclerosis
Not Provided
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
100
September 9, 2019
May 7, 2018   (Final data collection date for primary outcome measure)

Key Inclusion Criteria:

  • 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:

  • 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

Sexes Eligible for Study: All
16 Years to 85 Years   (Child, Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Belgium,   Canada,   France,   Germany,   Ireland,   Netherlands,   Switzerland,   United Kingdom,   United States
Italy
 
NCT02611674
999AS003
No
Not Provided
Not Provided
Biogen
Biogen
Not Provided
Study Director: Medical Director Biogen
Biogen
September 2017