Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001115729
Ethics application status
Approved
Date submitted
2/08/2022
Date registered
12/08/2022
Date last updated
12/08/2022
Date data sharing statement initially provided
12/08/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Multiple sclerosis exercise mode and intensity study
Scientific title
The effect of a continuous versus interval hybrid functional electrical stimulation exercise intervention on cardiorespiratory response in people with advanced multiple sclerosis.
Secondary ID [1] 307697 0
None
Universal Trial Number (UTN)
U1111-1281-1436
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 327243 0
Condition category
Condition code
Neurological 324385 324385 0 0
Multiple sclerosis
Physical Medicine / Rehabilitation 324386 324386 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The main purpose of the study will be to assess exercise capacity, cardiorespiratory and power outcomes on two modes of exercise during three different exercise protocols. The results will allow us to understand how to elicit higher intensities of exercise in people with advanced multiple sclerosis (MS).

Familiarization: Participants will perform six familiarization sessions with functional electrical simulation (FES) cycling and arm crank ergometry (ACE). Electrical stimulation will be applied via gel electrodes on the front and back of the quadriceps, hamstring, and gluteal muscle groups to cause these muscles to contract and pedal the stationary cycle. Each familiarization session will be 1.5 hours in duration, including set up and exercise. These sessions will be performed prior to the exercise trials over a three to six week period and the final session will occur in the week before the first exercise trial.

The electrical stimulation will be increased over 10 minutes in each session to a level at which can be tolerated by each participant. Participants will then arm crank exercise for 20 minutes. This will include two sessions of each exercise trial, that is, 20 minutes exercise at a rate of perceived exertion (RPE) of 12 – 13, interval exercise with 60 second work and 30 seconds rest at a RPE of 14 – 17 and interval exercise with 4 minutes work and 3 minutes rest at a RPE of 14 – 17.

For each exercise capacity test and exercise trial, the electrical stimulation will be increased over 10 minutes for the FES trials and will remain at 100% of the pre-determined maximum stimulation tolerated during familiarization. Each session will be supervised by an Exercise and Sports Science Australia Accredited Exercise Physiologist. Each trial will be separated by three days to one week.

Exercise capacity tests: Participants will perform two incremental exercise tests in a randomized order to determine peak VO2 and power. Exercise modes will include ACE and ACE combined with FES cycling (hybrid FES cycling).

Exercise trials: Participants will perform six exercise trials in a randomized order with cardiorespiratory measures (such as VO2, heart rate) and power as the main outcome measures. An average of the peak power data obtained in the ACE incremental test and hybrid FES cycling incremental test will be used to determine the percentage of peak arm crank Watts to be performed in Hybrid and ACE trials. These percentages of peak workload have been chosen to ensure the same amount of total arm crank work (Watts x time) is performed during each trial.
1. Hybrid FES cycling continuous trial: 10 mins of FES increase, then 20 minutes comprising:
20 minutes arm cranking at 45% of peak arm crank power, 12-13 RPE, FES at 100% tolerance
2. Hybrid FES cycling interval trial 1: 10 mins of FES increase, then 14.5 minutes comprising:
60 seconds work / 30 seconds passive rest, 90% of peak arm crank power, 10 intervals (i.e. repetitions) of work/rest, 14 – 17 RPE, FES at 100% tolerance
3. Hybrid FES cycling interval trial 2: 10 mins of FES increase, then 25 minutes comprising:
4 minutes arm crank work (60 sec work at 75% peak arm crank power / 60 sec work at 85% peak arm crank power / 120 sec work at 90% peak arm crank power), 3 minutes passive rest between work period, 4 repetitions of work/rest, 14 – 17 RPE, FES at 100% tolerance
4. ACE continuous trial: 20 minutes comprising: 20 minutes arm cranking at 45% of peak arm crank power, 12-13 RPE
5. ACE interval trial 1: 14.5 minutes comprising: 60 seconds work/ 30 seconds passive rest, 90% of peak arm crank power, 10 repetitions of work/rest, 14 – 17 RPE
6. ACE interval trial 2: 25 minutes comprising: 4 minutes arm crank work (60 sec work at 75% peak arm crank power / 60 sec work at 85% peak arm crank power / 120 sec work at 90% peak arm crank power), 3 minutes passive rest between work period, 4 repetitions of work/rest, 14 – 17 RPE

Participants will be familiarized to FES cycling, arm cranking and RPEs prior to the exercise trials. Participants will be instructed and encouraged to achieve target power and RPE outcomes during the exercise trials.
Intervention code [1] 324172 0
Lifestyle
Comparator / control treatment
Arm crank ergometry. Arm crank ergometry exercise trials (trials 4 - 6) will serve as the comparator treatment.
Control group
Active

Outcomes
Primary outcome [1] 332192 0
Peak heart rate during each exercise trial. Measured by Polar OH1 optical heart rate monitor arm strap
Timepoint [1] 332192 0
Continuous measurement exercise capacity tests exercise trial 1 to 6.
Primary outcome [2] 332193 0
Peak oxygen consumption during each exercise trial. Measured by MGC Diagnostics Ultima Series metabolic cart
Timepoint [2] 332193 0
Continuous measurement during exercise capacity tests and exercise trials 1 - 6.
Secondary outcome [1] 412501 0
ACE power output in Watts as recorded by the MOTOmed ergometer.
Timepoint [1] 412501 0
Continuous measurement during exercise capacity tests and exercise trials.
Secondary outcome [2] 412504 0
FES cycling power output in Watts as recorded by the MOTOmed ergometer.
Timepoint [2] 412504 0
Continuous measurement during exercise capacity tests and exercise trials.
Secondary outcome [3] 412586 0
Feasibility: 7 Point Likert Scale
Timepoint [3] 412586 0
Participants will complete brief surveys to assess their perceptions. Participants will be asked how much they liked / disliked the exercise trial at the end of each trial.
Secondary outcome [4] 412588 0
Enjoyment: 7 Point Likert Scale
Timepoint [4] 412588 0
Participants will complete brief surveys to assess their perceptions. Participants will be asked
how likely they might undertake the mode / intensity in an ongoing training program at the end of each trial.
Secondary outcome [5] 412589 0
Fatigue: 7 Point Likert Scale
Timepoint [5] 412589 0
Participants will be asked how fatigued they feel at the end of each trial (after 1 minute rest ad 5 minutes rest) and 24 hours after each trial. (7 point Likert scale).

Eligibility
Key inclusion criteria
Are aged between 18 and 70 years old
Have been given a diagnosis of multiple sclerosis with and EDSS of 6.0 to 8.0
Have not experienced an multiple sclerosis exacerbation in the past three months
Are medically stable and with no changes in medication used for MS in the past three months
Ability to perform arm crank exercise with at least one arm
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Absolute contraindications to exercise testing as defined by the American College of Sports Medicine, for example, unstable angina, uncontrolled cardiac arrhythmias, or severe heart failure. Temporary contraindications may include uncontrolled hypertension, diabetes or recent heart attack, fracture, musculoskeletal injury or surgery, seizure or stroke, until stable.
Clinical evidence of any comorbid disease that may interfere with the ability to undertake the testing planned, including substance use disorder, psychosis, suicidality or significant cognitive impairment
Pregnant or are currently contemplating pregnancy
Contraindications to functional electrical stimulation such as cardiac demand pacemaker, or temporary exclusions until stable (e.g., healing fracture or chronic skin irritation)

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
The power calculations for this study are based on limited research comparing hybrid exercise with arm cranking ergometry in people with MS and the exploratory nature of this study. Recent research (Pilot Study of Enhancing Cardiorespiratory Exercise Response in People With Advanced Multiple Sclerosis With Hybrid Functional Electrical Stimulation, Mate et al 2021) involving people with advanced MS compared the difference in average heart rate between Hybrid (128 ± 21 bpm) and arm cranking (105 ± 18 bpm) showed an effect size of 1.16 when calculated using G*Power 3.1.9.4. Heart rate has been chosen as the basis for the main hypothesis, and therefore power calculation, as it is readily measured in laboratory and clinical settings and can be used as an indicator of intensity during aerobic exercise. Moderate intensity exercise is required for gains in aerobic fitness. On the basis of a power calculation an a of 0.05, a 1-ß of 0.80, and an effect size of 1.16 for one of the main outcome variables of detecting a difference in peak HR between hybrid interval and arm crank interval exercise, 8 participants will be needed. We will aim to recruit 10 participants (20% more participants) to account for potential data collection error and or drop-outs during the study.

Data will be checked for normality by being inspected visually and performing Kolmogorov-Smirnov tests. A two-way repeated measures ANOVA (repeated measures analysis of variance) will be performed to assess if the mode and or intensity of exercise has had an effect on the main outcome measures (eg, heart rate, VO2, power). The Friedman ANOVA test will be used if data are found not to be normally distributed.
Age, gender and potentially other factors that may influence the results, for example, controlling for comorbidities or medication. ANCOVA Models adjusted for these covariates will be used to explore differences between hybrid and ACE exercise modes and interval and continuous protocols. The level of statistical significance will be set at p < 0.05 and trends declared at p = 0.05–0.10.

The Pearson correlation coefficient will be used to assess the relationships between cardiorespiratory output (VO2, HR), arm crank power (Watts) , stimulation tolerated (mA) and MS status (EDSS, phenotype). Strength of relationships will be qualitatively assessed using the following criteria: trivial (r < 0.1), weak (r > 0.1 to 0.3), moderate (r > 0.3 to 0.5), and strong (r > 0.5 to 0.7), very strong (r > 0.7 to 0.9), nearly perfect (r > 0.9), and perfect (r = 1.0).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
2/07/2021
Date of last participant enrolment
Anticipated
29/07/2023
Actual
Date of last data collection
Anticipated
29/09/2023
Actual
Sample size
Target
10
Accrual to date
6
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 311965 0
University
Name [1] 311965 0
The University of Sydney
Country [1] 311965 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
D18 - Susan Wakil Health Building
Western Avenue
The University of Sydney
NSW 2006
Country
Australia
Secondary sponsor category [1] 313466 0
None
Name [1] 313466 0
Address [1] 313466 0
Country [1] 313466 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311394 0
Human Research Ethics Committee, The University of Sydney
Ethics committee address [1] 311394 0
Ethics committee country [1] 311394 0
Australia
Date submitted for ethics approval [1] 311394 0
03/12/2019
Approval date [1] 311394 0
17/05/2021
Ethics approval number [1] 311394 0
2021/064

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120942 0
Dr Ché Fornusek
Address 120942 0
D18 - Susan Wakil Health Building
Western Avenue
The University of Sydney
NSW 2006
Country 120942 0
Australia
Phone 120942 0
+61 2 9351 9200
Fax 120942 0
Email 120942 0
[email protected]
Contact person for public queries
Name 120943 0
Ché Fornusek
Address 120943 0
D18 - Susan Wakil Health Building
Western Avenue
The University of Sydney
NSW 2006
Country 120943 0
Australia
Phone 120943 0
+61 2 9351 9200
Fax 120943 0
Email 120943 0
[email protected]
Contact person for scientific queries
Name 120944 0
Ché Fornusek
Address 120944 0
D18 - Susan Wakil Health Building
Western Avenue
The University of Sydney
NSW 2006
Country 120944 0
Australia
Phone 120944 0
+61 2 9351 9200
Fax 120944 0
Email 120944 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual data will not be shared. Deidentified participant data will be aggregated and used in manuscripts for scientific journals.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.