Electrical Impedance Myography as an Outcome Measure in Amyotrophic Lateral Sclerosis Clinical Trials

Electrical Impedance Myography as an Outcome Measure in ALS Clinical Trials

Trials evaluating new therapies for stopping or slowing the progression of ALS depend critically upon the use of outcome measures to assess whether a potential treatment is effective. The more effective an outcome measure, the fewer patients need to be enrolled and the shorter the trial. Many outcome measures have been used over the years, including strength assessments, breathing tests, functional status surveys, and nerve testing, but all are far from ideal. A new method, called electrical impedance myography (EIM) appears to be especially promising in that it provides very consistent data from one testing session to the next, is sensitive to the muscle deterioration that occurs in ALS, and is entirely painless and non-invasive. In this study, investigators from multiple institutions plan to compare several different outcome measures, including EIM, in approximately 120 ALS patients, with each patient being followed for a period of one year. All of these measures will be compared to one another and an assessment of their ability to detect disease progression made. Our goal will be to determine whether EIM can serve as a valuable new outcome measure, ultimately leading to substantially faster, more effective ALS trials requiring fewer patients.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis

• Study Type: Observational
• Enrollment (Actual): 89

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
  • Georgia
    • Atlanta, Georgia, United States
      • Emory University
  • Maryland
    • Baltimore, Maryland, United States
      • Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02446
      • Beth Israel Deaconess Medical Center
  • New York
    • Syracuse, New York, United States
      • Upstate Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with amyotrophic lateral sclerosis (ALS)

Description

Inclusion Criteria:

• Definite or probably ALS by El Escorial criteria
• Muscle strength of at 3.5 in one limb

Exclusion Criteria:

• Forced vital capacity of less than 70%
• Atypical forms of motor neuron disease (monomelic amyotrophy, primary lateral sclerosis)
• Pacemaker

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
ALS patients; Patients with clinically established amyotrophic lateral sclerosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electrical Impedance Myography	The main outcome measure was the coefficient of variation (CoV) in the rate of the decline for each measure over time. The CoV was calculated by dividing the standard deviation in the rate of decline across the group of subjects and dividing that by the mean rate of decline for the cohort. This approach was taken for each of the measures being evaluated (ALS Functional Rating Scale-Revised, Handheld dynamometry, Electrical impedance myography). The lower the CoV in the rate of decline, the more sensitive it is to identifying a potential treatment effect, since it suggests gives a measure of homogeneity of the rate of decline across the population as well as the overall rate of decline. The smaller the standard deviation across the group and the larger the mean rate of decline across the group, the lower the CoV and the fewer number of subjects needed for a potential clinical trial using that outcome measure.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ALS Functional Rating Scale	The main outcome measure was the coefficient of variation (CoV) in the rate of the decline for each measure over time. The CoV was calculated by dividing the standard deviation in the rate of decline across the group of subjects and dividing that by the mean rate of decline for the cohort. This approach was taken for each of the measures being evaluated (ALS Functional Rating Scale-Revised, Handheld dynamometry, Electrical impedance myography). The lower the CoV in the rate of decline, the more sensitive it is to identifying a potential treatment effect, since it suggests gives a measure of homogeneity of the rate of decline across the population as well as the overall rate of decline. The smaller the standard deviation across the group and the larger the mean rate of decline across the group, the lower the CoV and the fewer number of subjects needed for a potential clinical trial using that outcome measure.	6 months
Handheld Dynamometry	The main outcome measure was the coefficient of variation (CoV) in the rate of the decline for each measure over time. The CoV was calculated by dividing the standard deviation in the rate of decline across the group of subjects and dividing that by the mean rate of decline for the cohort. This approach was taken for each of the measures being evaluated (ALS Functional Rating Scale-Revised, Handheld dynamometry, Electrical impedance myography). The lower the CoV in the rate of decline, the more sensitive it is to identifying a potential treatment effect, since it suggests gives a measure of homogeneity of the rate of decline across the population as well as the overall rate of decline. The smaller the standard deviation across the group and the larger the mean rate of decline across the group, the lower the CoV and the fewer number of subjects needed for a potential clinical trial using that outcome measure.	6 months

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: ALS Association
• Investigators: Principal Investigator: Seward B Rutkove, MD, Beth Israel Deaconess Medical Center; Principal Investigator: Jeremy M Shefner, MD, PhD, Upstate Medical Center

Publications and helpful links

General Publications

• Rutkove SB, Zhang H, Schoenfeld DA, Raynor EM, Shefner JM, Cudkowicz ME, Chin AB, Aaron R, Shiffman CA. Electrical impedance myography to assess outcome in amyotrophic lateral sclerosis clinical trials. Clin Neurophysiol. 2007 Nov;118(11):2413-8. doi: 10.1016/j.clinph.2007.08.004. Epub 2007 Sep 25.

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: February 9, 2008
• First Submitted That Met QC Criteria: February 20, 2008
• First Posted (Estimate): February 21, 2008

Study Record Updates

• Last Update Posted (Estimate): September 25, 2014
• Last Update Submitted That Met QC Criteria: September 13, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: biomarker; amyotrophic lateral sclerosis; motor neuron disease; impedance; outcome measure
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: EIMALS