Comparison of Vigorous Versus Low Intensity Cool Room Treadmill Training in People with Multiple Sclerosis

Training to Restore Walking and Promote Nervous System Repair in Multiple Sclerosis: RCT to Determine the Importance of Intensity

New research in animal models of MS suggests that greater training intensity is required to restore lost functions. We have developed and tested vigorous intensity cool room treadmill training that people with MS who have fatigue and heat-sensitivity can tolerate. This study will focus on the appropriate dosage of training.

Study Overview

• Status: Withdrawn
• Conditions: Multiple Sclerosis; Neurological Rehabilitation; Exercise; Neuronal Plasticity; Cooling
• Intervention / Treatment: Other: Body-weight supported treadmill training in a room cooled to 16°C

Detailed Description

Our previous research showed that vigorous aerobic training in a room cooled to 16°C can improve walking and measures of brain plasticity among people with MS related walking disability, especially in those who had fatigue and heat sensitivity. As a next step, we will compare our novel vigorous intensity cool room treadmill training to low intensity cool room treadmill walking and determine whether intensity is important in order to improve brain repair and restore walking among people with MS. Our first objective is to compare the effects of 12 weeks of vigorous versus low intensity training on walking. Our second objective is to determine whether treadmill training alters indicators of brain repair. We hypothesize that the cool room vigorous training will result in greater increases in walking and less fatigue, which will be sustained at follow-up. We also hypothesize that improvements will align with less brain inhibition (shortened CSP measured using Transcranial Magnetic Stimulation) and greater upregulation of the neurotrophin IGF-1.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1A 1E5
      • Memorial University of Newfoundland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• people with a confirmed diagnosis of relapsing-remitting or progressive MS
• older than 18 and less than 70 years of age
• able to walk at least 10 meters with use of walking aids (Expanded Disability Status Scale (EDSS) <7.0)
• must be stable without relapse for at least 90 days

Exclusion Criteria:

• currently attending physical rehabilitation
• functional community ambulators (gait speed>120 cm/s)
• a relapse of MS

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low Intensity Group; Less than 40% Heart Rate Reserve	Other: Body-weight supported treadmill training in a room cooled to 16°C; Exercise will be performed on a treadmill using an overhead harness for safety in a temperature controlled-room at 16°C with 1:1 supervision. The high intensity group will maintain vigorous intensity with a target workload >60% of heart rate reserve for 30 min (plus 5min warm up and 5min cool down) while the low-intensity group will walk at mild intensity (<40% heart rate reserve) for the same duration. Heart rate, blood pressure, and rating of perceived exertion will be recorded throughout to monitor for potential adverse events and to ensure that target training zone heart rates are maintained. The intervention is 3 times per week for 12 weeks, with a 3-month run-in observational period to confirm disease stability, and 3-month follow-up to determine the sustainability of effects.
Experimental: Vigorous Intensity Group; More than 60% Heart Rate Reserve	Other: Body-weight supported treadmill training in a room cooled to 16°C; Exercise will be performed on a treadmill using an overhead harness for safety in a temperature controlled-room at 16°C with 1:1 supervision. The high intensity group will maintain vigorous intensity with a target workload >60% of heart rate reserve for 30 min (plus 5min warm up and 5min cool down) while the low-intensity group will walk at mild intensity (<40% heart rate reserve) for the same duration. Heart rate, blood pressure, and rating of perceived exertion will be recorded throughout to monitor for potential adverse events and to ensure that target training zone heart rates are maintained. The intervention is 3 times per week for 12 weeks, with a 3-month run-in observational period to confirm disease stability, and 3-month follow-up to determine the sustainability of effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fast walking speed	Gait velocity (cm/s) measured while walking at fast pace	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spatiotemporal parameters of gait measured while walking at self-selected pace	Walkway outputs include step length and width (cm), double support time (%), symmetry (ratio between affected and less-affected sides)	Following completion of the 12-week exercise intervention and 3-months post-exercise intervention
Maximal oxygen consumption during graded exercise test	VO2max	Following completion of the 12-week exercise intervention and 3-months post-exercise intervention
Multiple Sclerosis Impact Scale-29	The Multiple Sclerosis Impact Scale-29 provides physical and psychological sub-scales. Using a Likert scale, participants indicate the degree to which problems, such as 'moving about' and 'balance' affect them from 'not at all' to 'extremely'.	Following completion of the 12-week exercise intervention and 3-months post-exercise intervention
Fatigue Severity Scale	A 9-item questionnaire, which assesses the severity of fatigue with items scored on a 7-point scale, '1 = strongly disagree' and '7 = strongly agree'. The minimum and maximum score possible are 9 and 63 respectively. Another reporting method is the mean of all scores from all 9-items, with minimum and maximum score possible being 1 and 7 respectively.	Following completion of the 12-week exercise intervention and 3-months post-exercise intervention
Hospital Anxiety and Depression Scale	A self-reported rating scale of severity of mood symptoms ranging from 0-21 with higher score indicating more symptoms.	Following completion of the 12-week exercise intervention and 3-months post-exercise intervention
Montreal Cognitive Assessment	Measures overall cognitive function with score ranging from 0 to 30 with higher scores indicating higher executive function	Following completion of the 12-week exercise intervention and 3-months post-exercise intervention
Symbol Digit Modality Test	Cognitive impairment	Following completion of the 12-week exercise intervention and 3-months post-exercise intervention
Transcranial Magnetic Stimulation	Corticospinal excitability	Following completion of the 12-week exercise intervention and 3-months post-exercise intervention
Serum Insulin-like growth factor-1 (IGF-1)	Resting and exercise-induced serum levels of IGF-1 in response to the 12-week exercise intervention	Following completion of the 12-week exercise intervention and 3-months post-exercise intervention
Structural and functional brain changes on Magnetic Resonance Imaging (MRI)	Standardized protocol recommended by the Canadian Dementia Imaging Group (https://www.cdip-pcid.ca/) which includes T1 and T2-weighted structural images, diffusion tensor imaging, and resting state connectivity.	Following completion of the 12-week exercise intervention and 3-months post-exercise intervention

Collaborators and Investigators

• Sponsor: Memorial University of Newfoundland
• Collaborators: Multiple Sclerosis Society of Canada
• Investigators: Principal Investigator: Michelle Ploughman, PhD, Memorial University of Newfoundland

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2030
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: November 19, 2019
• First Submitted That Met QC Criteria: November 20, 2019
• First Posted (Actual): November 22, 2019

Study Record Updates

• Last Update Posted (Actual): November 27, 2024
• Last Update Submitted That Met QC Criteria: November 25, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: 20201156

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No