Quantitative Fatigue and Muscle Performance in Multiple Sclerosis

Fatigue is consistently rated as the top symptomatic complaint for individuals with multiple sclerosis (MS). Currently, the MS Fatigue Impact Scale (MFIS), a subsection of the Multiple Sclerosis Quality of Life (MSQoL), is the clinical standard used by neurologists for monitoring and tracking fatigue in individuals with MS. However, fatigue is multidimensional phenomenon and subjective measures have had poor or limited relationships with functional status. While previous study has focused on contributing factors to fatigue such as sleep disorders and diminished cortical excitability, this line of inquiry has neglected the role of muscle structure and function on fatigue in every day functional tasks. An alternative approach is to assess quantitative fatigue using anaerobic testing methods. However, more knowledge is needed to understand the role that quantitative fatigue plays in self-reported fatigue measures and function of daily activities. Our purpose is to determine the association between quantitative fatigue tests with performance-based measures of mobility and self-reported health-related quality of life. Our secondary goal is to understand how the intrinsic properties of muscle tissue influence muscle performance in Veterans with MS.

Study Overview

• Status: Unknown
• Conditions: Multiple Sclerosis; Fatigue

Detailed Description

Participants will complete study assessments at the DC VAMC. Disease severity will be assessed by medical staff completing the EDSS. Peak torque assessment for the knee flexors and extensors will be performed on an isokinetic dynamometer (Biodex System 4). Muscle morphology measures of the rectus femoris will be obtained using diagnostic musculoskeletal B-mode ultrasound (Phillips EPIQ 7 180 Plus) with a 10 Mhz linear transducer. The sonographic measures will include muscle thickness and echogenicity. The mode of exercise testing and the type of muscle action will influence the assessment of fatigue. Therefore, isokinetic fatigue measures for the knee extensors will be assessed on separate visits (at least 48 hours apart). Performance-based measures of function will include an assessment of patient mobility and the 25-foot walk test. Muscle power will be estimated by the timed sit to stand test. Subjective measures of fatigue and quality of life include the MSQoL, MFIS, and Neurology Quality of Life Adult Fatigue Bank (AFB).

• Study Type: Observational
• Enrollment (Actual): 30

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Men and women between the ages of 20 and 85 years (n=30) with a history of multiple sclerosis (Expanded Disability Status Scale, EDSS < 7.0) will be consecutively recruited from the DC VAMC Neurology Service and Multiple Sclerosis Center of Excellence.

Description

Inclusion Criteria:

• A male or female Veteran participant must have a medical diagnosis of multiple sclerosis
• Veteran will be between the ages of 20 and 85 years old

Exclusion Criteria:

• Veterans with an EDSS score > 7.0
• Veterans with any cardiac condition that may cause sudden decompensation during exertional fatigue testing (e.g., severe congestive heart failure and uncontrolled hypertension)
• Veterans found to have severe depression (BDI score >28)
• Veterans with lower extremity amputation
• Steroid Infusion less than 2 weeks prior to enrollment
• Veterans with a lower extremity joint replacement
• Veterans that exhibit severe cognitive impairment
• Defined as loss of orientation to person, place and/or time and an inability to follow three step commands.
• Veterans that are unable to perform a stand pivot transfer with minimal assist

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Multiple Sclerosis Fatigue (MSF) Cohort; Participants will complete study assessments over 4 visits to the DC VAMC. Disease severity will be assessed by the EDSS, and a cognitive battery will be completed. Peak torque assessment for the knee flexors and extensors will be performed on an isokinetic dynamometer (Biodex System 4). Muscle morphology measures of the rectus femoris will be obtained using diagnostic musculoskeletal ultrasound. The sonographic measures will include muscle thickness and echogenicity. Isokinetic and isoinertial mode fatigue measures for the knee extensors will be assessed on separate visits (at least 48 hours apart). Performance-based measures of function will include an assessment of patient mobility and the 25-foot walk test. Muscle power will be estimated by the timed sit to stand test. Subjective measures of fatigue and quality of life include the MSQoL, MFIS, and Neurology Quality of Life Adult Fatigue Bank (AFB).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue Index	Initial visit	Day 1
Maximal Volitional Contraction	Initial visit	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Adult Myopathy Assessment Tool	Initial visit	Day 1
25 foot walk Test	Initial visit	Day 1
Chair Stand Test	Initial visit	Day 1
Modified Fatigue Impact Scale	Initial visit	Day 1
Multiple Sclerosis Quality of Life	Initial visit	Day 1
Adult Fatigue Bank	Initial visit	Day 1
Ultrasound caliper measure of rectus femoris thickness	Initial visit	Day 1
Ultrasound image post-processing of rectus femoris grayscale	Initial visit	Day 1

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kurtzke Expanded Disability Status Scale	Initial visit	Day 1

Collaborators and Investigators

• Sponsor: Washington D.C. Veterans Affairs Medical Center

Publications and helpful links

General Publications

• Seamon BA, Harris-Love MO. Clinical Assessment of Fatigability in Multiple Sclerosis: A Shift from Perception to Performance. Front Neurol. 2016 Nov 7;7:194. doi: 10.3389/fneur.2016.00194. eCollection 2016. No abstract available.

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): October 1, 2018
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: August 2, 2016
• First Submitted That Met QC Criteria: September 21, 2016
• First Posted (Estimate): September 23, 2016

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 12, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Fatigue
• Other Study ID Numbers: MRIB 01772