Clinical Trial: Study and Treatment of Visual Dysfunction and Motor Fatigue in Multiple Sclerosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Study and Treatment of Visual Dysfunction and Motor Fatigue in Multiple Sclerosis

Brief Summary: Primary fatigue represents a major cause of disability in patients with multiple sclerosis (MS), being reported in about 90% of cases. Fatigue interferes with everyday functioning but, unfortunately, little is known about its mechanisms. The investigators propose a characteristic eye movement abnormality (internuclear ophthalmoparesis, INO), commonly encountered in MS, as a simple model for primary motor fatigue. The investigators described worsening of ocular performance in MS patients with INO following visual tasks (ocular motor fatigue), which is likely due to decreased neural conduction along brain pathways injured by MS. This mechanism could represent a major component of MS-related primary motor fatigue. Relevant to Veterans' care, INO is a significant cause of visual disability, especially when complicated by ocular fatigue, and limits daily activities such as reading and driving. The investigators propose a medical treatment to improve ocular performance/fatigue in INO, which can reduce visual disability and improve quality of life in Veterans with MS.

Detailed Summary:

This project focuses on fatigue, an extremely common yet poorly understood complaint in patients affected by multiple sclerosis (MS). Primary fatigue, that is fatigue not secondary to other MS-associated symptoms (e.g., sleep disorder or depression), is a distinct clinical entity and a cause of severe disability in most patients. As fatigue limits everyday activities and interferes with exercise-based rehabilitation, understanding its mechanisms is crucial to improving function and quality of life of Veterans with MS. Primary fatigue is divided in two broad categories, mental (cognitive) and physical (motor) fatigue, the latter being the focus of this proposal. Evidence suggests that primary motor fatigue originates within the central nervous system (CNS) but, although several factors have been invoked (e.g., demyelination, axonal loss, inflammation), a neurophysiological model to explain its underlying mechanisms is still lacking.

First, with this project, the investigators propose a characteristic eye movement abnormality, internuclear ophthalmoparesis (INO), as a simple and accessible model for primary motor fatigue in MS. INO is a disorder of binocular coordination (conjugacy), in which fast eye movements (saccades) of the adducting eye (i.e., the eye moving towards the nose) are slow during horizontal gaze shifts, due to demyelination of a specific CNS pathway (the medial longitudinal fasciculus, MLF). Preliminary results in a small MS group of patients show that patients with INO exhibit changes in ocular conjugacy (i.e., ocular motor fatigue) during a 10-minute saccadic fatigue test, but normal subjects do not. The investigators hypothesize that ocular motor fatigue is representative of a major component of primary motor fatigue in MS, as it likely reflects deterioration of neural conduction fidelity along the demyelinated MLF axons. The investigators aim at showin
Sponsor: VA Office of Research and Development

Current Primary Outcome: Eye movement assessment [ Time Frame: baseline, after 4 weeks, after 6 weeks, after 10 weeks ]

Changes in binocular horizontal conjugacy of saccades at baseline and following the saccadic fatigue test, before and after treatment, using: 1) abducting/adducting eye ratio for saccadic peak velocity (pulse size ratio); 2) time difference in occurrence of peak acceleration in the adducting vs. the abducting eye (pulse time delay).


Original Primary Outcome: Changes in binocular horizontal conjugacy of saccades [ Time Frame: baseline, after 4 weeks, after 6 weeks, after 10 weeks ]

Changes in binocular horizontal conjugacy at baseline and following the saccadic fatigue test, before and after treatment, using: 1) abducting/adducting eye ratio for saccadic peak velocity (pulse size ratio); 2) time difference in occurrence of peak acceleration in the adducting vs. the abducting eye (pulse time delay).


Current Secondary Outcome:

  • Visual function assessment [ Time Frame: baseline, after 4 weeks, after 6 weeks, after 10 weeks ]
    1) MNREAD acuity charts for reading acuity and speed; 2) King-Devick test for saccades performance.
  • Gait assessment [ Time Frame: baseline, after 4 weeks, after 6 weeks, after 10 weeks ]
    1) 25-foot Walk Test.
  • Visual disability assessment [ Time Frame: baseline, after 4 weeks, after 6 weeks, after 10 weeks ]
    NEI-VFQ-25 and NOS.
  • Quality of life assessment [ Time Frame: baseline, after 4 weeks, after 6 weeks, after 10 weeks ]
    MS Quality of Life Inventory.


Original Secondary Outcome:

  • Changes in visual function [ Time Frame: baseline, after 4 weeks, after 6 weeks, after 10 weeks ]
    1) MNREAD acuity charts for reading acuity and speed; 2) King-Devick test for saccades performance.
  • Visual function assessment [ Time Frame: baseline, after 4 weeks, after 6 weeks, after 10 weeks ]
    1) MNREAD acuity charts for reading acuity and speed; 2) King-Devick test for saccades performance.
  • Gait assessment [ Time Frame: baseline, after 4 weeks, after 6 weeks, after 10 weeks ]
    1) 25-foot Walk Test; 2) 6-minute Walk Test.
  • Visual disability and quality of life assessment [ Time Frame: baseline, after 4 weeks, after 6 weeks, after 10 weeks ]
    1) NEI-VFQ-25 and NOS; 2) MS Quality of Life Inventory.


Information By: VA Office of Research and Development

Dates:
Date Received: March 3, 2015
Date Started: April 1, 2015
Date Completion: March 2018
Last Updated: April 6, 2017
Last Verified: April 2017