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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
  Purpose
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.

Condition
Amyotrophic Lateral Sclerosis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Methodology Study of Novel Electrophysiological, Physical, and Imaging Outcome Measures to Assess the Progression of Amyotrophic Lateral Sclerosis

Resource links provided by NLM:


Further study details as provided by Biogen:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 100
Actual Study Start Date: January 6, 2016
Estimated Study Completion Date: September 9, 2019
Estimated Primary Completion Date: May 7, 2018 (Final data collection date for primary outcome measure)
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   16 Years to 85 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Participants suffering from ALS are recruited by participating physicians in a standard clinical practice setting.
Criteria

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

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02611674


  Show 21 Study Locations
Sponsors and Collaborators
Biogen
Investigators
Study Director: Medical Director Biogen
  More Information

Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02611674     History of Changes
Other Study ID Numbers: 999AS003
First Submitted: October 8, 2015
First Posted: November 23, 2015
Last Update Posted: September 4, 2017
Last Verified: September 2017

Additional relevant MeSH terms:
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases