Exercise and Progressive Multiple Sclerosis

Sponsor

University of Regina (Other)

Overall Status

Recruiting

CT.gov ID

NCT05496881

Collaborator

First Steps Wellness Centre (Other), Saskatchewan Health Research Foundation (Other), University of Saskatchewan (Other)

Enrollment

Location

Arms

28.6

Anticipated Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A growing body of work suggests that regular exercise can support symptom management and improve physical function for people living with progressive multiple sclerosis (MS). However, the best type of exercise to improve physical function and promote positive changes in the central nervous system in people with progressive MS is not well characterized. Here, the investigators have designed a clinical trial that compares the effects of distinct exercise protocols on aspects of physical function, physical fitness, and central nervous system function in people living with progressive MS.

Condition or Disease	Intervention/Treatment	Phase
Progressive Multiple Sclerosis	Other: Exercise Group 1 Other: Exercise Group 2 Other: Exercise Group 3	N/A

Detailed Description

A total of 69 participants with progressive multiple sclerosis (MS) and moderate motor disability in the province of Saskatchewan, Canada will be randomly assigned to receive one of three distinct exercise programs. All exercise programs will be delivered three times per week in 60-minute group sessions over the course of 12 weeks under the supervision of Clinical Exercise Physiologists. Exercise programming will include activities focused on mobility, fitness, and flexibility. Assessments of physical function, physical fitness, and central nervous system function will be conducted immediately before, after, and six weeks following completion of the exercise programs.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

69 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

All interventions will involve 60-minute sessions delivered three times per week for 12 weeks. All interventions will involve the whole body but differ in content.All interventions will involve 60-minute sessions delivered three times per week for 12 weeks. All interventions will involve the whole body but differ in content.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Participants will not be informed of the different study arms. Interventions will be scheduled to avoid contact between study arms. Participants will be asked to not describe their activities to those outside of their exercise group. Although it will not be possible to blind program instructors from the intervention that they deliver, instructors will not be aware of the expected results. Assessors and data analysts will be fully blinded to study arm allocation.

Primary Purpose:

Supportive Care

Official Title:

Evaluating Exercise Effects on Physical and Central Nervous System Function in People With Progressive Multiple Sclerosis

Actual Study Start Date :

Jun 15, 2022

Anticipated Primary Completion Date :

Mar 31, 2024

Anticipated Study Completion Date :

Oct 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exercise Group 1 The intervention will focus on mobility and balance.	Other: Exercise Group 1 Prescribed exercises will focus on mobility and balance.
Active Comparator: Exercise Group 2 This intervention will focus on physical fitness.	Other: Exercise Group 2 Prescribed exercises will focus on physical fitness.
Sham Comparator: Exercise Group 3 This intervention will focus on flexibility, range of motion, and muscle tone.	Other: Exercise Group 3 Prescribed exercises will focus on flexibility, range of motion, and muscle tone.

Arm

Intervention/Treatment

Experimental: Exercise Group 1

The intervention will focus on mobility and balance.

Other: Exercise Group 1

Prescribed exercises will focus on mobility and balance.

Active Comparator: Exercise Group 2

This intervention will focus on physical fitness.

Other: Exercise Group 2

Prescribed exercises will focus on physical fitness.

Sham Comparator: Exercise Group 3

This intervention will focus on flexibility, range of motion, and muscle tone.

Other: Exercise Group 3

Prescribed exercises will focus on flexibility, range of motion, and muscle tone.

Outcome Measures

Primary Outcome Measures

Timed 25-Foot Walk Test [6 weeks post intervention]
The Timed 25-Foot Walk Test provides an assessment of mobility and lower-extremity function through a measurement of fast walking speed. Test scores range from 0-180 seconds with higher values indicating a worse outcome.

Secondary Outcome Measures

Motor Evoked Potential Amplitude [6 weeks post intervention]
Measuring the amplitude of motor evoked potentials elicited by transcranial magnetic stimulation delivered over the motor cortex provides information about corticospinal excitability. Corticospinal excitability is a potential marker of MS disease burden that is responsive to physical training in people with MS and has been used to study experience-dependent neuroplasticity in other neurological conditions. The range of response amplitude is 0-100% of maximal muscle fibre recruitment, with higher values indicating better outcome.

Other Outcome Measures

Mini Balance Evaluation Systems Test [6 weeks post intervention]
The Mini Balance Evaluation Systems Test provides an assessment of balance control systems. The Mini-BESTest has a high sensitivity in detecting balance impairments in people with MS. The Mini-BESTest has score values between 0-28 with a higher score meaning a better outcome.
Multiple Sclerosis Impact Scale [6 weeks post intervention]
The Multiple Sclerosis Impact Scale is a self-report survey that measures the impact of multiple sclerosis on physical and psychological functioning. The MSIS test has a score value between 0-145 with a higher score meaning a worse outcome.
9-Hole Pegboard Test [6 weeks post intervention]
The 9-Hole Pegboard Test is a quantitative measure of upper extremity function. The test has a time limit of 300 seconds with higher values indicating a worse outcome.
Symbol Digit Modalities Test [6 weeks post intervention]
The Symbol Digit Modalities Test is used to asses divided attention, visual scanning, tracking and motor speed. The SDMT test is scored as the number of correct answers provided within 90 seconds (range: 0-110). A higher score would indicate a better outcome.
Peak Isometric Hand Grip Force [6 weeks post intervention]
Peak Isometric Hand Grip Force provides a measure of general upper-extremity strength. Values typically range from 0 to approximately 75 kilograms of force, with higher values indicating greater strength.
Peak Isometric Knee Extensor Torque [6 weeks post intervention]
Peak Isometric Knee Extensor Torque provides a measure of general lower-extremity strength. Values typically range from 0 to approximately 75 kg of force, with higher values indicating greater strength. Values typically range from 0 to approximately 300 Newton*Meters of torque, with higher values indicating greater strength.
Peak Oxygen Uptake [6 weeks post intervention]
Peak Oxygen Uptake provides a measure of cardiorespiratory fitness. It is measured through administration of a maximal exercise test. Values typically range from 0-90 milliliters per minute per kilogram.
Tumor Necrosis Factor Alpha concentration in systemic blood [6 weeks post intervention]
Tumor Necrosis Factor is an inflammatory cytokine that can be measured in human blood serum. Values typically range from 100 to 5000 picograms per milliliter of blood serum. Higher values are generally considered worse.
Brain-Derived Neurotrophic Factor in systemic blood [6 weeks post intervention]
Brain-Derived Neurotrophic Factor is a neurotrophic growth factor that can be measured in human blood serum. Values typically range from 15 to 80 nanograms per milliliter of blood serum. Higher values are generally considered better.
Neurofilament Light concentration in systemic blood [6 weeks post intervention]
Neurofilament Light is a neuronal cytoplasmic protein that can be measured in human blood serum. Values typically range from 0 to 100 picograms per milliliter of blood serum. Higher values are generally considered worse.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

diagnosis of progressive MS by a neurologist
physician clearance for exercise
a Patient-Determined Disease Steps (PDSS) score between 2 and 6 (i.e., moderate motor disability)
a Timed 25-Foot Walk (T25-FW) test time > 6.0 s.

Exclusion Criteria:

a baseline score >24 on the Godin-Shephard Leisure Time Physical Activity Questionnaire (i.e., high physical activity levels)
absolute contraindications to TMS (e.g. history of seizure)
a history of any neurological conditions other than MS
relapse in the past three months (self-reported, neurologist confirmed)
psychiatric diagnosis
substance abuse