Effects of Low-intensity Interval Walking With Blood Flow Restriction on Functional Capacity in Multiple Sclerosis

Effects of Low-intensity Interval Walking With Blood Flow Restriction on Gait Speed and Functional Impairments in Patients With Severe Multiple Sclerosis: a Pilot Study

The aim of the study is to evaluate the safety, feasibility and initial efficacy of an interval-based walking training at low speed performed with blood flow restriction (BFR) on gait speed and functional impairments in patients with Multiple Sclerosis (MS).

Patients with severe MS will be recruited at outpatient rehabilitation clinics (University Hospital of Ferrara). Eligible participants will be randomized to interval walking training with BFR (the experimental group) or conventional exercise therapy (the control group) according to a blocked-randomization stratified by gender with 1:1 ratio. Both groups will receive 12 rehabilitative sessions over 6 weeks, for a 2 sessions/week pattern.

The experimental group will undergo interval-based walking training at a slow speed according to a walk:rest ratio of 1:1 for a total of 6 minutes, to be repeated 5 times. Blood flow restriction, applied to the proximal thigh, will be set at a maximum of 40% of systolic blood pressure. The control group will be treated with conventional therapy.

Changes in gait speed, endurance, balance, lower limbs strength and quality of life will be assessed at baseline, at the end of training, and at follow up.

The proposed training modality has never been tested in patients with MS and, if the hypotheses were supported by the results, might be a novel tool to improve muscle strength with a positive impact on gait disabilities, balance and quality of life for patients with MS.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: BFR-Walking; Other: Conventional therapy

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Ferrara, Italy, 44124
    • University Hospital of Ferrara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• primary and secondary progressive MS patients according to the diagnostic MS criteria revised by Polman et al.
• Male and females, aged 18 to 65 years;
• Severe gait impairments, defined by an Expanded Disability Status Scale (EDSS) ranging from 5.5 to 6.5;
• Lack of MS worsening in the previous three months prior to the intervention period;
• Cognitive functioning to provide informed consent identified by a Mini-Mental Status Examination (MMSE) score = 24/30.

Exclusion Criteria:

• Neurologic conditions in addition to MS that may affect motor function and other medical conditions likely to interfere with the ability to complete safely the study protocol, independently from the group assignment;
• Considerable muscle spasticity, defined by a Modified Ashworth Scale (MAS) score > 3 or contractures that may limit range of motion or function for hip, knee or ankle flexors/extensor;
• Relapsing of MS-related conditions or changes in drug therapy or any other confounding factor during the study;
• Rehabilitation treatments or Botulinum toxin injections during the three months preceding the start of the study.
• Intermittent claudication and peripheral artery disease
• Contraindication to exercise training (e.g., unstable angina, congestive heart failure)

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: Conventional therapy	Other: Conventional therapy; Participants will perform 12 training sessions over 6 weeks. Patients will perform assisted over-ground walking for a total of around 40 minutes, inserted between a 10-minute warm-up and cool-down period. The patient will be encouraged by the same experienced physiotherapist to walk back and forth on 50-meter indoor flat corridor with their habitual walking device. Patient will be asked to walk without stopping until reaching an effort corresponding to a value of 8 out of 10 of the rating of perceived exertion (Borg scale). When the exertion level is reached, the patients will be allowed to rest sitting on a chair if necessary; after a suitable rest period, when patients express sufficient desire to start again, the training will restart
Experimental: BFR-Walking; Interval walking training with blood flow restriction.	Other: BFR-Walking; Participants will perform 12 training sessions over 6 weeks, including a 10-minute warm up and cool down period. Patients will perform 5 six-minute bouts of over ground intermittent walking exercise (1-minute walk/rest) with their habitual walking device at a prescribed speed maintained by a metronome, starting from 60 steps/minute. A fixed resting period of 3 minutes will follow each walking bout. During walking, participants will wear BFR bands at both tights. Before every walking bout, the bands will be tightened at a low intensity (max 40% of blood systolic pressure) and untied at the end of every walking bout when patients will be asked to grade their RPE (Borg Scale). Walking speed will be weekly increased by 3 steps/minute, if the previous level was well-tolerated by the patient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Timed 25-foot Walk test	The patient will be directed to one end of a clearly marked 25-foot course and will be instructed to walk 25 feet (7.62 m) as quickly as possible, but safely, using the prescribed assistive devices. The task is immediately administered again by having the patient walk back the same distance. The test will be performed according to the instructions reported on the manual of the National Multiple Sclerosis Society. To ensure an accurate and objective measure of the primary outcome, the time needed for each subject to complete the test will be collected with the aid of a photocells system with a precision of a millisecond and simultaneously by the assessors with a chronometer. The walking speed will be calculated as the mean of the two trials performed.	Baseline (prior to the first exercise session, T0); end of the treatment (after 6 weeks, T1); follow-up (after 12 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-Minute Walking Test	Subjects will be instructed to walk up and down as far as possible on a 22m walkway in six minutes without encouragement, with the possibility to slow down and rest if necessary. The total distance walked will be recorded.	Baseline (prior to the first exercise session, T0); end of the treatment (after 6 weeks, T1); follow-up (after 12 weeks)
Berg Balance Scale	To evaluate the ability to maintain balance statically or while performing functional movement. It includes 14 observable tasks common to an everyday life measured on a 5-point ordinal scale.	Baseline (prior to the first exercise session, T0); end of the treatment (after 6 weeks, T1); follow-up (after 12 weeks)
5-time Sit-to-Stand test	Patient stand on a 43-cm chair with his/her arms folded across the chest and the back against the chair. Then the patient will be instructed as follow: "I want you to stand up and sit down 5 times as quickly as you can". The time to complete the 5 repetitions will be recorded.	Baseline (prior to the first exercise session, T0); end of the treatment (after 6 weeks, T1); follow-up (after 12 weeks)
Multiple Sclerosis Impact Scale	This is a 29-item self-report measure with 20 items associated with a physical function scale and 9 items with a psychological function scale. Items ask about the impact of MS on everyday life in the past two weeks with possible answers set on a 1-5 Likert scale. Each of the two scales is converted to a 0-100 scale where a score of 100 indicates a greater impact of disease on daily function.	Baseline (prior to the first exercise session, T0); end of the treatment (after 6 weeks, T1); follow-up (after 12 weeks)
Fatigue Severity Scale	The scale consists of answering short questions that require the subject to read each statement and rate his or her level of fatigue from 1 to 7, depending on how appropriate they felt the statement applied to them over the preceding week.	Baseline (prior to the first exercise session, T0); end of the treatment (after 6 weeks, T1); follow-up (after 12 weeks)
Short Form Health Survey 36	This is a generic measurement to assess health-related quality of life. It consists of 8 sub-scales with a score ranging from 0-100 used separately as outcome measures of various aspects of health-related-quality of life. It also measures two main health concepts: physical and mental health.	Baseline (prior to the first exercise session, T0); end of the treatment (after 6 weeks, T1); follow-up (after 12 weeks)

Collaborators and Investigators

• Sponsor: University Hospital of Ferrara
• Investigators: Principal Investigator: Fabio Manfredini, MD, University Hospital of Ferrara

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2018
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): December 30, 2019

Study Registration Dates

• First Submitted: May 18, 2018
• First Submitted That Met QC Criteria: May 18, 2018
• First Posted (Actual): June 1, 2018

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: February 3, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: rehabilitation; mobility; exercise therapy; blood flow restricted exercise
• 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
• Other Study ID Numbers: 170783

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data that underlie the results published at the end of the trial after deidentification. The database of the study will be published in a public repository.
• IPD Sharing Time Frame: IPD will be available beginning 6 months following study results publication.
• IPD Sharing Access Criteria: Anyone who wishes to access the data
• IPD Sharing Supporting Information Type: Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No