Methodology Study of Novel Outcome Measures to Assess Progression of ALS

NCT02611674 | Completed

• 1 other identifier: 999AS003
• Study Type: observational
• Target: 138
• Locations: 9 countries
• Sites: 21

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.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (7)

• 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

  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.

  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.

  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.

  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.

  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.

  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.

  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

  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 MUNE

  Day 1 and Day 7

• 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 HHD

  Day 1 and Day 7

Eligibility Criteria

• Age: 16 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants suffering from ALS are recruited by participating physicians in a standard clinical practice setting.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Biogen: lead

Study Sites (21)

University of California San Diego Medical Center

San Diego, California, 92103, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

The Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital, MA

Charlestown, Massachusetts, 2129, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, EC037, United States

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Montreal Neurological Institute Clinical Research Unit

Montreal, Quebec, H3A 2B4, Canada

Location

Hopital Gui de Chauliac, Service de Neurologie

Montpellier, Hérault, 34295, France

Location

Groupe Hospitalier Pitie-Salpetriere

Paris, Paris, 75013, France

Location

Charite - Campus Virchow-Klinikum

Berlin, 13125, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitaetsklinikum Jena

Jena, 07743, Germany

Location

Universitaetsklinikum Ulm

Ulm, 89081, Germany

Location

Beaumont Hospital

Dublin, Dublin 9, Ireland

Location

UMC Utrecht

Utrecht, CX, 3584, Netherlands

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Royal Hallamshire Hospital

Sheffield, West Midlands, S102JF, United Kingdom

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2015
• First Posted: November 23, 2015
• Study Start: January 6, 2016
• Primary Completion: July 27, 2018
• Study Completion: August 1, 2019
• Last Updated: October 24, 2019

Record last verified: 2019-10

Locations

BE (1); GB (1); CA (2); DE (4); NL (1); US (8); IE (1); FR (2); CH (1)