Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000088842p
Ethics application status
Submitted, not yet approved
Date submitted
13/11/2020
Date registered
1/02/2021
Date last updated
1/02/2021
Date data sharing statement initially provided
1/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of a short burst of high-intensity exercise versus moderate-intensity exercise combined with restriction to blood flow to the exercising leg muscles on cardiovascular health in people with a combination of risk factors of cardiovascular disease (metabolic syndrome)
Scientific title
The acute and chronic effects of reduced exertion high-intensity interval training versus blood flow restriction exercise on central arterial stiffness and other novel cardiovascular health indices in adults with metabolic syndrome: a pilot randomised waitlist-control study
Secondary ID [1] 302781 0
None
Universal Trial Number (UTN)
U1111-1261-1482
Trial acronym
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
metabolic syndrome 319728 0
Condition category
Condition code
Metabolic and Endocrine 317662 317662 0 0
Metabolic disorders
Cardiovascular 317663 317663 0 0
Other cardiovascular diseases
Physical Medicine / Rehabilitation 317961 317961 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Thirty males and females (aged 30 to 65 years) with metabolic syndrome (MetS) will be recruited and randomised to participate in either the: i) reduced exertion high-intensity interval training [REHIT]; ii) moderate-intensity exercise with blood flow restriction (BFR moderate-intensity exercise); and iii) waitlist control.

This trial will consist of two phases. The first phase will require the participants to attend one supervised training session to determine the acute effect of the exercise interventions. Assessments will include measures of central arterial stiffness, metabolic syndrome severity, cardiorespiratory fitness, and cardiac autonomic function. Participants will then enter the second phase of the trial and will continue with the same exercise program from Phase 1, but conducted 2-4 times per week (Weeks 1-2 = 2 days; Weeks 3-4 = 3 days; Weeks 5-8 = 4 days) until the 8-week follow-up. Following Phase 2, participants from the waitlist control group will be re-randomised into either of the exercise groups. The participants will be tested at baseline, after a single exercise session, and after 8 weeks follow-up. Written informed consent will be obtained from all participants before inclusion. All participants will receive verbal and written information about their exercise training intervention.

Intervention (Exercise Training)
The study will consist of 2 exercise intervention groups; 1) REHIT and 2) BFR moderate-intensity exercise. All exercise sessions will be supervised by Accredited Exercise Scientists in groups (maximum of 3 participants per Accredited Exercise Scientist) within the participants' workplace. Exercise heart rate (HR), RPE, and volume (intensity, duration, and frequency) during the trial will be monitored and recorded. HR and RPE will be monitored via a HR monitor (Polar Electro, Kempele, Finland) and the Borg 6-20 RPE scale, respectively. Attendance and compliance with the interventions will also be recorded in a logbook.

Exercise Interventions

REHIT
CAR.O.LTM cycle ergometer units developed by Integrated Health Partners (London, UK; https://carolfitai.com/) will be placed in the workplace environments in order for participants to conveniently perform the exercise intervention. Each REHIT session will utilize the intense 10-min ride option on the cycle ergometer consisting of a 3 min warm-up, 20 s sprint, 3 min active recovery (slow pedal), 20 s sprint, and 3 min cool-down.

BFR moderate-intensity exercise
Each BFR moderate-intensity exercise session (10 min) will follow the same format as REHIT, which will also consist of a 3 min warm-up, 20 s sprint, 3 min active recovery (slow pedal), 20 s sprint, and 3 min cool-down on a cycle ergometer. The target HR will be established in the following manner: Target HR = HR range of 10-20 bpm (above VT1 and below VT2). Pressure cuffs (~18 cm wide) will be applied on the proximal portion of both thighs as per the current guideline. The cuff belts will be inflated to 140 mmHg during the 20 s sprints of the protocol and deflated during all other periods (warm-up, active recovery, cool-down periods)
Intervention code [1] 319061 0
Treatment: Other
Comparator / control treatment
Waitlist control
Participants in this group will continue with daily activities and will be re-randomized into one of the exercise training interventions after 8 weeks.
Control group
Active

Outcomes
Primary outcome [1] 325713 0
Primary outcome 1: central arterial stiffness
Pulse wave analysis will be measured using an automated device (SphygmoCor, AtCor Medical Pty Ltd., West Ryde, Australia) to assess arterial stiffness and central blood pressure indices. For pulse wave analysis, a cuff will be placed around the arm between the elbow and shoulder, and will be partially inflated to obtain a measure of central blood pressure.
Timepoint [1] 325713 0
Timepoint: Baseline, after a single exercise session, and after 8 weeks
Primary outcome [2] 326216 0
Primary outcome 2: central arterial stiffness
Pulse wave velocity will be measured using an automated device (SphygmoCor, AtCor Medical Pty Ltd., West Ryde, Australia) to assess arterial stiffness. For pulse wave velocity, a cuff will be placed around the upper thigh, and a pen-like tonometer pressure sensor on the participant’s neck to derive a measure of arterial stiffness.
Timepoint [2] 326216 0
Timepoint: Baseline, after a single exercise session, and after 8 weeks
Secondary outcome [1] 388884 0
Secondary outcome: Metabolic syndrome severity (MetS severity)
MetS severity is determined from tests conducted in a 12-hr fasted state: i) resting brachial systolic and diastolic blood pressure (manual sphygmonamoter); lipid profile (high-density lipoprotein cholesterol [HDL-C] and triglycerides [TRG] and fasting glucose) (via fingerprick blood sample analysed using the LDX Cholestech machine) ; and iii) anthropometric measures (waist circumference [WC], body mass index [BMI]). MetS severity will be presented as sex-specific MetS z-score to be calculated using the following equations: i) MetS z-scoremen = [(40 - HDL-C)/8.9] + [(TG - 150/69)] + [(FG -
100)/17.8] + [(WC - 102)/11.5] + [(MAP - 100)/ 10.1]; (2)MetS z-scorewomen = [(50 - HDLC)/14.5] + [(TG - 150/69)] + [(FG - 100)/17.8] + [(WC - 88)/12.5] + [(MAP - 100)/10.1],
Timepoint [1] 388884 0
Timepoint: Baseline, after a single exercise session, and after 8 weeks
Secondary outcome [2] 388885 0
Secondary outcome 2: glycemic control
A small sample of blood (~24mL) will be drawn from the participant’s antecubital vein after a 12-hour overnight fast to assess glycemic control (HbA1c [via Quo-Test HbA1c analyser and insulin resistance [via HOMA2-IR calculator]) and pancreatic beta cell function (proinsulin). Qualified and experienced phlebotomists will conduct this procedure.
Timepoint [2] 388885 0
Timepoint: Baseline, after a single exercise session, and after 8 weeks
Secondary outcome [3] 388886 0
Secondary outcome 3: inflammation
A small sample of blood (~24mL) will be drawn from the participant’s antecubital vein after a 12-hour overnight fast to assess inflammatory markers (IL-22, HsCRP, TNF-a, interleukin-6 [IL-6], and IL-10). Qualified and experienced phlebotomists will conduct this procedure.
Timepoint [3] 388886 0
Timepoint: Baseline, after a single exercise session, and after 8 weeks
Secondary outcome [4] 388887 0
Secondary Outcome 4: body composition
Height, weight, waist circumference, and hip circumference will be assessed using current technical recommendations (Coombes and Skinner, 2014). The measuring tools to be used are stadiometers, weighing scales, and anthropometric tape measures, respectively.
Timepoint [4] 388887 0
Timepoint: Baseline, after a single exercise session, and after 8 weeks
Secondary outcome [5] 388888 0
Secondary outcome 5: cardiorespiratory fitness
Cardiorespiratory fitness (VO2peak) will be assessed via indirect calorimetry using an individualized graded maximal cycling exercise protocol. Ventilation, oxygen and carbon dioxide concentrations will be measured directly during the test via a metabolic cart. Following an appropriate warm-up, the work rate (i.e. treadmill speed) is progressively increased every minute until the participant can no longer continue [volitional fatigue]. The test lasts approximately 10-15 minutes. Blood pressure, heart rate rhythm (via electrocardiogram) and RPE will be monitored throughout the test to ensure safety of participants.
Timepoint [5] 388888 0
Timepoint: Baseline, after a single exercise session, and after 8 weeks
Secondary outcome [6] 388889 0
Secondary outcome: cardiac autonomic function
Following 15 minutes of rest in a supine position, heart rate will be recorded continuously for 5 minutes using a heart rate monitor (Polar Electro, Kempele, Finland) to obtain a ‘heart rate variability’ measure.
Timepoint [6] 388889 0
Timepoint: Baseline, after a single exercise session, and after 8 weeks

Eligibility
Key inclusion criteria
Inclusion Criteria:

-Male and female (age 30 to 65 years)
-Diagnosed with MetS according to the IDF criteria
-Be willing to participate in either of the interventions
-Be cleared to undertake either exercise intervention
-Engaged in less than 150 minutes of moderate-intensity exercise/physical activity per week
-be willing to undergo a pre-exercise screening evaluation according to the Australian Pre-exercise Screening System (APSS) (SMA 2005) and cleared to undertake either exercise program
Minimum age
30 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:
-Have been sent for medical clearance, based on the APSS screening guidelines, and clearance to participate is not provided.
-Diagnosed with either Type 1 or 2 diabetes
-Smokers or have a history of smoking within the past 2 years
-Consume 2 standard alcohol beverages per day
-Pregnant
-Participants with pacemakers
-Unstable angina
-Recent myocardial infarction (last 4 weeks)
-Severe valvular heart disease
-Uncompensated heart failure
-Pulmonary disease
-Uncontrolled hypertension
-Kidney failure
-Cardiomyopathy
-Medications likely to affect insulin sensitivity (i.e. glucocorticoids, oral contraceptives, sulfonylureas, etc.)
-Orthopaedic limitations prohibiting engagement in physical activity

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
allocation concealed

sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)

Stratified by age and gender
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size calculation: A sample size calculation was completed using a non-inferiority sample size calculator (https://www.sealedenvelope.com/power/continuous-noninferior/). If there is truly no difference between the study interventions (REHIT versus BFR exercise), then 30 participants (10 in each group) are required to be 80% sure that the lower limit of a one-sided 95% confidence interval (or equivalently a 90% two-sided confidence interval) will be above the non-inferiority limit of -1. The non-inferiority limit of -1 was based on the reported clinically meaningful improvement in central arterial stiffness represented by the PWV of 1 m/s. The standard deviation (SD) of the primary outcome (PWV; SD=1.1 m/s) entered into the sample size calculator was based on a previous study following a similar exercise intervention.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
22/02/2021
Actual
Date of last participant enrolment
Anticipated
30/08/2021
Actual
Date of last data collection
Anticipated
31/12/2021
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment postcode(s) [1] 31991 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 307198 0
University
Name [1] 307198 0
Flinders University
Country [1] 307198 0
Australia
Primary sponsor type
University
Name
Flinders University
Address
Sturt building, Sturt campus, Flinders University, Bedford park, SA 5042
Country
Australia
Secondary sponsor category [1] 307811 0
None
Name [1] 307811 0
N/A
Address [1] 307811 0
N/A
Country [1] 307811 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 307306 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 307306 0
Ethics committee country [1] 307306 0
Australia
Date submitted for ethics approval [1] 307306 0
17/02/2020
Approval date [1] 307306 0
Ethics approval number [1] 307306 0

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

Contacts
Principal investigator
Name 106766 0
Dr Joyce Ramos
Address 106766 0
Sturt Building, South Wing, Room S268, Flinders University, Sturt Road, Bedford Park South Australia 5042
Country 106766 0
Australia
Phone 106766 0
+61 8 8201 3272
Fax 106766 0
Email 106766 0
[email protected]
Contact person for public queries
Name 106767 0
Joyce Ramos
Address 106767 0
Sturt Building, South Wing, Room S268, Flinders University, Sturt Road, Bedford Park South Australia 5042
Country 106767 0
Australia
Phone 106767 0
+61 8 8201 3272
Fax 106767 0
Email 106767 0
[email protected]
Contact person for scientific queries
Name 106768 0
Joyce Ramos
Address 106768 0
Sturt Building, South Wing, Room S268, Flinders University, Sturt Road, Bedford Park South Australia 5042
Country 106768 0
Australia
Phone 106768 0
+61 8 8201 3272
Fax 106768 0
Email 106768 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


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.