Methodology Study of Novel Outcome Measures to Assess Progression of ALS

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02611674
• Other study ID #: 999AS003
• Status: Completed
• Start date: January 6, 2016
• Est. completion date: August 1, 2019

Study information

• Verified date: October 2019
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: August 1, 2019
• Est. primary completion date: July 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven
Canada	Montreal Neurological Institute Clinical Research Unit	Montréal	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
France	Hopital Gui de Chauliac, Service de Neurologie	Montpellier	Hérault
France	Groupe Hospitalier Pitie-Salpetriere	Paris cedex 13	Paris
Germany	Charite - Campus Virchow-Klinikum	Berlin
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitaetsklinikum Jena	Jena
Germany	Universitaetsklinikum Ulm	Ulm
Ireland	Beaumont Hospital	Dublin
Netherlands	UMC Utrecht	Utrecht	CX
Switzerland	Kantonsspital St. Gallen	St. Gallen
United Kingdom	Royal Hallamshire Hospital	Sheffield	West Midlands
United States	The Emory Clinic	Atlanta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Massachusetts General Hospital, MA	Charlestown	Massachusetts
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of California San Diego Medical Center	San Diego	California
United States	California Pacific Medical Center	San Francisco	California
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Ireland,  Netherlands,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Within-participant test-retest reliability between the 2 repeated measurements occurring on Day 1 and Day 7 for EIM		Day 1 and Day 7
Secondary	Within-participant test-retest reliability between the 2 repeated measurements for CMAP		Day 1 and Day 7
Secondary	Within-participant test-retest reliability between the 2 repeated measurements for MUNE		Day 1 and Day 7
Secondary	Within-participant test-retest reliability between the 2 repeated measurements for MUNIX		Day 1 and Day 7
Secondary	Within-participant test-retest reliability between the 2 repeated measurements for HHD		Day 1 and Day 7
Secondary	Within-participant test-retest reliability between the 2 repeated measurements for SVC		Day 1 and Day 7
Secondary	Within-participant test-retest reliability between the 2 repeated measurements for ALSFRS-R		Day 1 and Day 7
Secondary	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
Secondary	Comparison between 6-month changes for muscle electrophysiological measures		Baseline to Month 12
Secondary	Comparison between 6-month changes for muscle strength measures		Baseline to Month 12
Secondary	Comparison between 6-month changes for functional measures		Baseline to Month 12
Secondary	Comparison of molecular biomarkers with disease progression		Baseline to Month 12