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Completed

NCT Number: NCT02611674

Methodology Study of Novel Outcome Measures to Assess Progression of ALS

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.

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Key information

Conditions

Amyotrophic Lateral Sclerosis Central Nervous System Diseases Metabolic Diseases Motor Neuron Disease Nervous System Diseases Neurodegenerative Diseases Neuromuscular Diseases Nutritional and Metabolic Diseases Proteostasis Deficiencies Spinal Cord Diseases TDP-43 Proteinopathies

Age range

16 year–85 year

Sex eligibility

All sexes

Study type

Observational

Primary location

UZ Leuven, Leuven, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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 outcomes

  1. 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

  2. Within-participant test-retest reliability between the 2 repeated measurements for CMAP

    Time frame: Day 1 and Day 7

  3. Within-participant test-retest reliability between the 2 repeated measurements for MUNE

    Time frame: Day 1 and Day 7

  4. Within-participant test-retest reliability between the 2 repeated measurements for MUNIX

    Time frame: Day 1 and Day 7

  5. Within-participant test-retest reliability between the 2 repeated measurements for HHD

    Time frame: Day 1 and Day 7

  6. Within-participant test-retest reliability between the 2 repeated measurements for SVC

    Time frame: Day 1 and Day 7

  7. Within-participant test-retest reliability between the 2 repeated measurements for ALSFRS-R

    Time frame: Day 1 and Day 7

  8. 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

  9. Comparison between 6-month changes for muscle electrophysiological measures

    Time frame: Baseline to Month 12

  10. Comparison between 6-month changes for muscle strength measures

    Time frame: Baseline to Month 12

  11. Comparison between 6-month changes for functional measures

    Time frame: Baseline to Month 12

  12. Comparison of molecular biomarkers with disease progression

    Time frame: Baseline to Month 12

Sponsors and collaborators

Lead sponsor

Biogen

Industry

Registry information

Official study title

Methodology Study of Novel Electrophysiological, Physical, and Imaging Outcome Measures to Assess the Progression of Amyotrophic Lateral Sclerosis

Important dates

Study start
2016
Primary completion
2018
Study completion
2019
First posted
Nov 23, 2015
Registry last updated
Oct 24, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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