Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000876594
Ethics application status
Approved
Date submitted
1/07/2024
Date registered
18/07/2024
Date last updated
18/07/2024
Date data sharing statement initially provided
18/07/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Resistance exercise and artery function
Scientific title
The effect of resistance exercise with and without the Valsalva manoeuvre on central arterial stiffness and cerebral autoregulation in healthy sedentary individuals
Secondary ID [1] 312416 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atherosclerosis 334234 0
Stroke 334336 0
Condition category
Condition code
Cardiovascular 330900 330900 0 0
Normal development and function of the cardiovascular system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The interventions for the current study are moderate intensity resistance exercise (RE) and Valsalva manoeuvres (described below). The current study is separated into 4 visits that are designed to test the physiological responses to RE, Valsalva manoeuvres (VM), and a combination of both. Each participant will complete all 4 visits (no separate arms), and at no point will the participant or researchers be blinded to the requirements of that visit. The first visit is a familiarisation and screening session, designed to determine the eligibility of a participant, answer any questions the participant may have, gain consent from the participant, and familiarise the participant with all study procedures. The following 3 visits will be completed in a randomised order and are designed to determine the effect of the interventions individually, and in combination. However, for simplicity the visits are ordered to indicate the different requirements and are labelled as follows:
• Visit 2 – RE only
• Visit 3 – RE and VM
• Visit 4 – VM only

For each visit, the main outcomes of interest are the change in the physiological variables (e.g. pulse wave velocity) from pre-intervention (e.g. prior to resistance exercise) to post-intervention (e.g. following resistance exercise) for each participant (a within-subject design).
All study 4 visits will occur face-to-face, in a temperature-controlled laboratory, and be conducted a senior researcher with extensive research experience and 20 years of RE experience. The first visit will take ~1 hour and the reaming 3 visits will take ~2 hours. Each visit will be separated by at least 5 days.

The information collected will include the following:

Demographics
(Visit 1)
• Date of birth, age, sex
• Height and weight
• Participant contact details
• Current exercise regimen
Medical history
(Visit 1)
• Other medical conditions and medications
• Smoking history: smoking status (ex, current, never)
• Females: self-reported pregnancy status and menstrual cycle phase
All visits
• Adverse events
• Serious adverse events

Weight and height
Height will be measured at visit 1 using a stadiometer and weight with electronic weighing scales. Participants will take off their shoes for both measurements.

Pulse wave velocity (PWV)
Carotid-femoral PWV will be measured using a high-fidelity tonometer (SphygmoCor, AtCor Medical). The measurement of PWV requires a concurrent electrocardiogram (3 lead) and brachial blood pressure (BP) measurements. The right common carotid and femoral pulses will be palpated. The strongest pulse point for both arteries will be marked, and the straight-line distance from this mark to the suprasternal notch will be measured using a tape measure. The tonometer will then be placed first over the right common carotid artery and be adjusted to obtain the strongest waveform, data will be collected for 10s. The process will be repeated for the femoral artery. Once successful carotid and femoral values have been obtained the Sphygomocor Software Suite (AtCor Medical) will generate an absolute PWV value in m/s. Duplicate measurements will be performed both pre- and post-completion of the visit requirements in visits 2, 3 and 4. If the duplicate measurements differ by >0.5 m/s a third measurement will be performed. All measurements will be completed by the same trained investigator.

Middle cerebral artery blood velocity
Middle cerebral artery blood velocity (MCAv) will be measured using transcranial Doppler Ultrasonography (Doppler-BoxX, DWL Compumedics) as a proxy for cerebral blood flow. Bilateral middle cerebral arteries will be insonated for the purposes of assessing cerebrovascular function.

Dynamic cerebral autoregulation (dCA)
Dynamic cerebral autoregulation (dCA) will be assessed using squat-stand manoeuvres (SSM). To quantify dCA continuous (beat-to-beat) measurements of BP and MCAv are required. Non-invasive beat-to-beat measurement of BP will be recorded via finger photoplethysmography (Human NIBP NANO, ADInstruments) and MCAv will be measured as described above. dCA measurements will be performed both pre- and post-completion (immediately after PWV measures in each instance) of the visit requirements in visits 2, 3 and 4.
For the SSM, each participant will complete 2 bouts of SSM generating BP oscillations at 2 distinct frequencies - 0.05 Hz (20 s cycle: 10 s squat followed by 10 s standing) and 0.10 Hz (10 s cycle: 5 s squat followed by 5 s standing) that are timed by metronome. During the squatting phase each participant will perform a body weight squat (no additional load) until 45 degrees of knee flexion is achieved. The participant will hold this position (for either 5s or 10s), and then stand (for 5s or 10s). The participant will repeat this cyclic manoeuvre at each frequency (0.05 Hz or 0.1 Hz) for 5 minutes, with each bout of SSM separated by 5 minutes of seated rest. Additionally, heart rate will be measured via three lead electrocardiogram and partial pressure of end tidal carbon dioxide will be measured via nasal cannula to account for the influence of arterial carbon dioxide content on cerebral blood flow.

Valsalva Manoeuvre (VM)
All VMs completed in the current study will have a target mouth pressure (intensity) of 40 mm Hg. During the familiarisation session and visit 4 participants will be asked to blow into a cardboard mouthpiece that is connected to a calibrated pressure transducer with the achieved pressure displayed to the participant in real-time. The VMs that do not meet the target pressure will still be counted and contribute to the overall total.
In visit 3 where RE will be performed with a VM, the VM will be performed during the concentric phase only during the last 6 repetitions of each set, for all exercises (see below).
During visit 4 (VM only) participants will complete a total of 72 VMs performed across 12 ‘sets’. Each set will consist of 6 short VMs of 3s, separated by 2s breaks. The timing of the VM and breaks will be given verbally by the research team. Each set of VMs will be separated by 3 minutes of rest. The total number of VMs performed during visits 3 and 4 is matched at 72 and will be counted by the research team.

Resistance Exercise (RE)
The exercise loading for this study is 60% of the estimated 1 repetition maximum (1RM). The estimation of the 1RM for bicep curl, leg extension, leg press, and chest press will be completed within the familiarisation session (visit 1). Using the number of repetitions completed, and the load lifted, the 1RM can be estimated using Brzycki’s equation. During the determination of the 1RM for each exercise, the participant will complete sets of <10 repetitions of a self-selected submaximal load. The load will then be increased gradually across multiple sets such that the participant fatigues prior to completing 10 repetitions. Each set and exercise will be separated by 3 minutes of recovery time.

During visits 2 and 3, participants will complete 3 sets of 10 repetitions for bicep curl, leg extension, leg press, and chest press at 60% of the 1RM value achieved in visit 1 (60%1RM). Each set will be separated by 3 minutes of rest. All sets and reps will be counted by the research tea. The bicep curl exercise will be completed first using a dumbbell whilst seated. The remaining exercises will be completed in a random order using Life Fitness exercise machines that will be adjusted to fit the participant. The breathing techniques (e.g. VM or continued ventilation) for each session where RE is performed is outlined below. Participants will be coached in the familiarisation session, and verbally instructed/reminded of the breathing requirements and exercise technique during visits 2 and 3.

Visit 2 – RE only
During this session:
• Participants will perform 3 sets of 10 repetitions of bicep curl, leg press, leg extension and chest press at 60%1RM. Each repetition will be timed to a metronome, with 2s for both the eccentric and concentric phases (4s per repetition). The participant will be asked to exhale during the eccentric phase of the movement and inhale during the concentric phase.

Visit 3 – RE and VM
During this session:
• Participants will perform 3 sets of 10 repetitions of bicep curl, leg press, leg extension and chest press at 60%1RM. Each RE repetition will be timed to a metronome, with 2s for both the eccentric and concentric phases (4s per repetition). The participant will be asked to exhale during the eccentric phase of the movement and inhale during the concentric phase. During the last 6 repetitions of each set the participant will be verbally instructed to perform a VM during the concentric phase of each exercise, generating a mouth pressure of ~40 mm Hg (no real-time feedback i.e. estimated).

Participant information and education
Resistance exercise technique
All resistance exercise will be first demonstrated to the participants in visit 1 a senior researcher with 20 years of resistance training experience. Following the demonstration of the correct technique, the participants will be able to practice the movements without additional load prior to the estimation of their 1RM. Only when correct technique is demonstrated will additional load be applied. Feedback regarding exercise technique will be provided throughout all visits by the investigators, and all RE will be supervised. The investigators will also be able to assist the participant should they fatigue and be unable to lift the load during any visit.

Diet recall
Participants will be asked to repeat their diet for the 12 hours prior to visit 2, 3 and 4. As visits 2, 3 and 4 are randomised, the participant will be asked to keep a diet diary for the 12 hours prior to whichever of visits 2, 3 and 4 occurs first, and then repeat this diet prior to remaining visits. Participants will be provided with a food recall diary at visit 1 and a list of vasoactive foods that should be avoided prior to each visit. Adherence to the diet requirements will be self-reported. The diet diary will be returned at the final study visit.

Restrictions prior to all visits:
• Strenuous exercise and alcohol for 12 hours, and caffeine (e.g. coffee, tea, or energy drinks) for 4 hours, prior to arriving at the laboratory.

Foods to avoid 12 hours prior to your laboratory visit:
• Beetroot and beetroot juice
• Dark chocolate
• Berries including blackcurrants and grapes
• Nutritional supplements containing high nitrate or anthocyanin content
Intervention code [1] 328922 0
Prevention
Intervention code [2] 328923 0
Lifestyle
Comparator / control treatment
Due to the within-subject, pre-post design design, each participant will serve as their own control. The RE only condition will serve as the control.
Control group
Active

Outcomes
Primary outcome [1] 338660 0
Carotid-femoral pulse wave velocity
Timepoint [1] 338660 0
Before (Pre) and immediately following (Post) completion of the visit requirements in visits 2 (RE only), 3 (RE and VM), and 4 (VM only).
Secondary outcome [1] 436888 0
Dynamic cerebral autoregulation
Timepoint [1] 436888 0
Before (Pre) and following (Post) completion of the visit requirements (immediately following measurement of pulse wave velocity) in visits 2 (RE only), 3 (RE and VM), and 4 (VM only).

Eligibility
Key inclusion criteria
- Aged between 18 and 35
- Do not partake in regular resistance exercise (RE), defined as having not completed (greater than 1 session per week for 3 consecutive weeks) dedicated resistance training (powerlifting, weightlifting, bodybuilding, or CrossFit) in the last 6 months
- Do not regularly perform rowing type exercise (greater than 1 session per week for 3 consecutive weeks) in the last 6 months. Rowing exercise produces similar sinusoidal fluctuations in blood pressure and MCAv to RE and may confer some of the same vascular adaptations. Perform less than or equal to 1 dedicated aerobic exercise session per week for greater than or equal to 6 months prior to the experiment. This does not include regular physical activity e.g. activities that would be classified as low intensity such as walking, gardening, low intensity cycling (commuting) and general household chores.
Minimum age
18 Years
Maximum age
35 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Self-reported diagnosis of any heart (e.g. congestive heart failure), vascular (e.g. atherosclerosis of peripheral vascular disease) or cerebrovascular (e.g. stroke) condition
• Have recently fainted (within the last 6 months), have repeated bouts of syncope of any origin, postural hypotension or postural orthostatic tachycardia syndrome
• Self-reported diagnosis of a pulmonary disease (e.g. chronic obstructive pulmonary disease (COPD))
• Self-reported diagnosis of a metabolic disease (e.g. diabetes mellitus)
• Self-reported diagnosis of a musculoskeletal or other soft tissue injury that may inhibit the completing of resistance exercise (e.g. previous fractures, or ligament, tendon, or muscle sprains/tears/inflammation)
• Have been told by their doctor that they should not exercise for any reason
• Are pregnant
• Currently smoke or vape, or have done so in the last 6 months
• Are taking any medications to control heart rate or blood pressure
• Have sensitive/irritable skin or a skin disease (infectious or non-infectious)
• Have any other reason to consider that they are not in good health and should not exercise
• Are unable to complete the exercises detailed in the study protocol (leg press, chest press, bicep curl, leg extension or squat stand)
• Any medical condition which, at the Investigator’s discretion, may present a safety risk or impact the feasibility of the study or study results.
• Additionally, participants will not be included in the study if the study team are unable to obtain an adequate blood velocity signal from the middle cerebral artery. The course of the middle cerebral artery can vary between individuals and obtaining an adequate signal in individuals with a tortuous middle cerebral artery can be difficult.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Trial order generated using simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
This is a crossover study where participants are not randomised into a group or treatment, instead the order of trials is randomised.
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2024
Actual
Date of last participant enrolment
Anticipated
1/04/2025
Actual
Date of last data collection
Anticipated
1/09/2025
Actual
Sample size
Target
15
Accrual to date
Final
Recruitment outside Australia
Country [1] 26398 0
New Zealand
State/province [1] 26398 0

Funding & Sponsors
Funding source category [1] 316829 0
University
Name [1] 316829 0
Massey University
Country [1] 316829 0
New Zealand
Primary sponsor type
University
Name
Massey University
Address
Country
New Zealand
Secondary sponsor category [1] 319062 0
None
Name [1] 319062 0
Address [1] 319062 0
Country [1] 319062 0
Other collaborator category [1] 283106 0
Other
Name [1] 283106 0
Eastern Institute of Technology | Te Pukenga
Address [1] 283106 0
Country [1] 283106 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315597 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 315597 0
Ethics committee country [1] 315597 0
New Zealand
Date submitted for ethics approval [1] 315597 0
27/05/2024
Approval date [1] 315597 0
11/06/2024
Ethics approval number [1] 315597 0
2024 EXP 19783

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

Contacts
Principal investigator
Name 135194 0
Dr Blake Perry
Address 135194 0
Massey University, Wallace Street, Mount Cook, Wellington 6021
Country 135194 0
New Zealand
Phone 135194 0
+6449793492
Fax 135194 0
Email 135194 0
[email protected]
Contact person for public queries
Name 135195 0
Blake Perry
Address 135195 0
Massey University, Wallace Street, Mount Cook, Wellington 6021
Country 135195 0
New Zealand
Phone 135195 0
+6449793492
Fax 135195 0
Email 135195 0
[email protected]
Contact person for scientific queries
Name 135196 0
Blake Perry
Address 135196 0
Massey University, Wallace Street, Mount Cook, Wellington 6021
Country 135196 0
New Zealand
Phone 135196 0
+6449793492
Fax 135196 0
Email 135196 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All de-identified data
When will data be available (start and end dates)?
Immediately following publication with no end date determined.
Available to whom?
Researchers who provide a sound proposal and at the discretion of the sponsor
Available for what types of analyses?
Meta analyses
How or where can data be obtained?
Upon reasonable request made to the the principal investigator via email - [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23934Ethical approval    388034-(Uploaded-01-07-2024-10-34-08)-HDEC letter of approval.pdf
23935Informed consent form    PIS-CF 388034-(Uploaded-01-07-2024-10-34-38)-RE and arterial function_PIS_CF_V1.0_latest.docx



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.