Methodology Study of Novel Outcome Measures to Assess Progression of ALS
- Conditions
- Amyotrophic Lateral Sclerosis
- Registration Number
- NCT02611674
- Lead Sponsor
- Biogen
- Brief 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 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 138
- 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
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Longitudinal standardized mean change in electrophysiological measures as assessed by motor unit number estimation (MUNE) 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 electrical impedance myography (EIM) 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 motor unit number index (MUNIX) 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 functional measures as assessed by Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) 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 compound muscle action potential (CMAP) 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 respiratory measures as assessed by slow vital capacity (SVC) 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 muscle strength measures as assessed by hand-held dynamometry (HHD) 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.
- Secondary Outcome Measures
Name Time Method Comparison between 6 and 12-month changes in exploratory measures with 18 and 24-month changes in ALSFRS-R and survival Baseline to Month 24 Within-participant test-retest reliability between the 2 repeated measurements for HHD Day 1 and Day 7 Comparison between 6-month changes for muscle electrophysiological measures Baseline to Month 12 Comparison between 6-month changes for muscle strength measures Baseline to Month 12 Within-participant test-retest reliability between the 2 repeated measurements for MUNIX Day 1 and Day 7 Within-participant test-retest reliability between the 2 repeated measurements for MUNE Day 1 and Day 7 Within-participant test-retest reliability between the 2 repeated measurements for SVC Day 1 and Day 7 Comparison between 6-month changes for functional measures Baseline to Month 12 Within-participant test-retest reliability between the 2 repeated measurements occurring on Day 1 and Day 7 for EIM Day 1 and Day 7 Within-participant test-retest reliability between the 2 repeated measurements for CMAP Day 1 and Day 7 Within-participant test-retest reliability between the 2 repeated measurements for ALSFRS-R Day 1 and Day 7 Comparison of molecular biomarkers with disease progression Baseline to Month 12
Trial Locations
- Locations (21)
University of California San Diego Medical Center
🇺🇸San Diego, California, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
The Emory Clinic
🇺🇸Atlanta, Georgia, United States
UZ Leuven
🇧🇪Leuven, Belgium
Massachusetts General Hospital, MA
🇺🇸Charlestown, Massachusetts, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Hopital Gui de Chauliac, Service de Neurologie
🇫🇷Montpellier, Hérault, France
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Montreal Neurological Institute Clinical Research Unit
🇨🇦Montréal, Quebec, Canada
Groupe Hospitalier Pitie-Salpetriere
🇫🇷Paris cedex 13, Paris, France
Charite - Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Universitaetsklinikum Jena
🇩🇪Jena, Germany
Beaumont Hospital
🇮🇪Dublin, Ireland
UMC Utrecht
🇳🇱Utrecht, CX, Netherlands
Universitaetsklinikum Ulm
🇩🇪Ulm, Germany
Kantonsspital St. Gallen
🇨🇭St. Gallen, Switzerland
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Royal Hallamshire Hospital
🇬🇧Sheffield, West Midlands, United Kingdom