Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000036718
Ethics application status
Approved
Date submitted
29/11/2021
Date registered
17/01/2022
Date last updated
17/01/2022
Date data sharing statement initially provided
17/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Physical activity and health: the effect of GoldFit YMCA participation on brain, breathing and blood pressure regulation in older adult humans - a longitudinal study.
Scientific title
Physical activity and health: the effect of GoldFit YMCA participation on central and peripheral chemoreflexes and cerebrovascular reactivity in older adult humans
Secondary ID [1] 305815 0
Nil known
Universal Trial Number (UTN)
U1111-1271-0241
Trial acronym
Linked study record
ACTRN12620001047987
This is a follow up study in a different study population (older adults and a community based exercise intervention). The design of this study has been informed by the methods developed and results of ACTRN12620001047987.

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular disease 324329 0
Condition category
Condition code
Cardiovascular 321946 321946 0 0
Coronary heart disease
Cardiovascular 321947 321947 0 0
Hypertension
Cardiovascular 321948 321948 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a non-therapeutic mechanistic physiological study.

All of the following procedures will be conducted by the doctoral candidate with assistance from a trained human physiologist staff member. The laboratory where all assessments will take place is located at the Human Physiology Laboratory, Department of Respiratory Physiology, Level 7 Auckland City Hospital, Auckland DHB.

Participants who are newly enrolled or intending to enroll in the GoldFit YMCA exercise training programme will undergo a one-on-one session with a qualified personal trainer to prescribe their individualized exercise training programme. During this session, participants will also perform baseline fitness assessment (6-minute walk test and 30s chair sit-to-stand). These assessments will be repeated at the end of the training period. Participants will attend a community-based exercise programme (GoldFit, YMCA, eight locations in Auckland), 3 times per week for 12 weeks. Participants will be asked to complete a 7-day physical activity recall questionnaire following each week of exercise training. The results of the 7-day physical activity recall questionnaire from each week of exercise training will be collated and used to monitor participant adherence.

All participants will undergo an initial visit to the laboratory where screening and familiarisation with all study protocol will take place. This visit will be ~60 minutes duration, and an investigator will explain the nature of the study procedures, answer and questions, and obtain written informed consent from the participant. Anthropometric (height, weight), demographic, general health and 7-day physical activity recall information will be obtained. Once enrolled in the study, participants will be briefly familiarised with the study procedures. To do this, participants will be instrumented for continuous monitoring of heart rate, blood pressure, oxygen saturation and respiration. Brain blood flow will not be measured at this visit.

The second visit will be an experimental session. Participants who are enrolling in the GoldFit YMCA exercise training programme will attend the laboratory for two identical experimental visits (~2 hours each). The first experimental visit will be scheduled ~2-7 days after the initial familiarisation visit, and prior to or within 1 week of beginning the GoldFit YMCA programme. The second experimental visit will be scheduled within 2 weeks of completion of 12 weeks of GoldFit exercise training.

At the experimental session, participants will be asked to sit in a comfortable armchair and remain in that position throughout the session. An intravenous catheter will be positioned in a superficial arm/hand vein, and a venous blood sample obtained (~20mL) by a trained researcher for analysis of blood glucose, cholesterol/lipids, and C-reactive protein. Participants will then be instrumented for continuous monitoring of heart rate, blood pressure, respiration and cerebral blood flow. More specifically, beat-to-beat blood pressure will be measured using finger photoplethysmography, using a small lightweight cuff wrapped around the finger and a cuff wrapped around the upper arm for calibration. Heart rate will be measured using standard electrocardiogram involving the placement of 3 sticky electrodes on the collarbones and chest (standard 3 lead ECG). Participants will wear a mouthpiece and nose clip to monitor respiration. Brain blood flow will be monitored using a transcranial Doppler ultrasound, with a probe placed over the temporal ‘window’ in front of the ear and above the zygomatic arch. The probe will be fixed in place using an adjustable headband and small amount of ultrasound gel.

After instrumentation, a 15-minute resting baseline will be observed with the last 5 minutes used for analysis, followed by chemoreflex assessment. Chemoreflex assessment will involve three breathing tests. Tests are separated by a 15-minute rest period. The first test is hyperoxic hypercapnia (CO2 rebreathing), used to evaluate central chemoreflex stimulation with diminished peripheral chemoreflex stimulation). The participant will then be coached using verbal feedback to hyperventilate in room air, until attaining an end tidal carbon dioxide concentration of ~25mmHg. Upon reaching this, the participant will be asked to perform a maximal expiration below functional residual capacity. Upon completion, the inspiratory source will be switched to a rebreathing bag filled with ~95% O2-~5% CO2, and the participant will be instructed to perform 5-6 deep and rapid breaths. Following this, the participant will be instructed to breath as required, until their end tidal carbon dioxide reaches ~55mmHg, signalling the end of the test. The second test is hyperoxia (100% O2), used to evaluate peripheral chemoreflex tonicity. Participants will perform four 1-minute exposures to hyperoxia, separated by 3-5 minutes. The third test is is isocapnic hypoxia (10% O2-90% N2), used to evaluate peripheral chemoreflex stimulation. The exposure will last 5 minutes, with end tidal oxygen of ~45mmHg and end tidal carbon dioxide of ~40mmHg maintained throughout the test.
Intervention code [1] 322297 0
Early detection / Screening
Comparator / control treatment
Participants who are recruited for the longitudinal arm of the study will act as their own controls, with within group pre- and post-12-weeks of GoldFit YMCA exercise training comparisons made.

All participants will receive the same treatment (three breathing tests per experimental session), and will also act as their own controls versus baseline values.
Control group
Active

Outcomes
Primary outcome [1] 329707 0
Central chemoreflex sensitivity (i.e., cardiorespiratory responses to hyperoxic hypercapnia).

Central chemoreflex sensitivity is assessed using hyperoxic hypercapnia (CO2 rebreathing, 5% CO2-95% O2). Cardiorespiratory variables are continuously recorded and central chemoreflex sensitivity is assessed as the change in ventilation per change in partial pressure of end tidal carbon dioxide (L/min/mmHg).
Timepoint [1] 329707 0
At baseline and at 12-weeks follow up.
Primary outcome [2] 329708 0
Peripheral chemoreflex sensitivity (i.e., cardiorespiratory responses to isocapnic hypoxia).

Peripheral chemoreflex sensitivity is assessed using isocapnic hypoxia. (10% O2-90% N2). Cardiorespiratory variables are continuously recorded and peripheral chemoreflex sensitivity is assessed as the absolute increase in ventilation from baseline expressed relative to the fall in oxygen saturation.
Timepoint [2] 329708 0
At baseline and at 12-weeks follow up.
Primary outcome [3] 329709 0
Peripheral chemoreflex tonicity (i.e., cardiorespiratory responses to intermittent hyperoxia).

Peripheral chemoreflex tonicity is assessed using intermittent exposure to hyperoxia (100% O2) and determined as the average of a single breath nadir for each of the four hyperoxic trials (ventilatory measures). For cardiovascular measures, 15s averages over the 1-minute hyperoxic exposure will be calculated, and a nadir 15s obtained. The average of the 15s nadir values for each of the four hyperoxic trials will be calculated.
Timepoint [3] 329709 0
At baseline and at 12-weeks follow up.
Secondary outcome [1] 403558 0
Cerebrovascular reactivity and cerebrovascular conductance.

Cerebrovascular reactivity and cerebrovascular conductance are assessed using the brain blood flow responses to hyperoxic hypercapnia and isocapnic hypoxia. Transcranial Doppler ultrasound is used to insonate the right middle cerebral artery. The slope of the relationship of velocity of the middle cerebral artery velocity (MCAv) and partial pressure of end tidal carbon dioxide gives cerebrovascular reactivity, and cerebrovascular conductance (CVCi) is calculated as MCAv divided by mean arterial pressure.
Timepoint [1] 403558 0
At baseline and at 12-weeks follow up.

Eligibility
Key inclusion criteria
- Aged >60 years old
- Men and women
- Free of chronic cardiovascular, respiratory, metabolic, or neurological disease
- Not currently engaging in regular exercise and have not been in a regular exercise routine for >12 months, and who are newly enrolled or intending to enroll to begin exercise training in the YMCA GoldFit exercise training programme, aged >60 years old
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• BMI <18 kg/m2
• Current smoker
• Current users of recreational drugs
• Current abusers of alcohol
• Recent (<12 month) history of hospital admission
• Significant arrhythmias (e.g., atrial fibrillation, previous VT / significant ventricular ectopy)
• Hemodynamically significant valvular heart disease (e.g., stenosis, mechanical valve replacement)
• Severe left ventricular systolic dysfunction
• Recent acute coronary syndrome (<12 months) (e.g., MI, angioplasty, unstable angina)
• Previous coronary artery bypass surgery
• Secondary causes of hypertension (e.g., phaeochromocytoma)
• Recent stroke/TIA (<12 months)
• Inability to fully or appropriately provide consent (e.g., language issue, reading capability)
• Underlying medical conditions, which in the opinion of the Investigator place the participant at unacceptably high risk for participating in the study.
Chronic and systemic illness including:
• Severe respiratory disease (e.g., chronic obstructive pulmonary disease);
• Severe, uncontrolled type II diabetes;
• Current treatment for cancer or complete remission <5 years
• Connective tissue or inflammatory disease
• Neurological / psychiatric disease (e.g., peripheral neuropathy, dementia, Parkinson’s, epilepsy)
• Infection or pyrexial illness
• Uncontrolled thyroid disorders
• Renal impairment (e.g., eGFR <60)
• Liver disease

Study design
Purpose of the study
Treatment
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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Other
Other design features
All participants will receive all interventions with CO2 rebreathing performed first, followed by intermittent hyperoxia and then isocapnic hypoxia.
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
Body mass index (BMI) will be expressed as the ratio between participant’s weight and the square of their height. Analogue signals for ECG, blood pressure, respiration (tidal volume, end tidal CO2 and O2, minute ventilation) and Vmean will be sampled simultaneously, with beat-to-beat or breath-by-breath time series obtained. Analogue signals for Vmean in the middle and posterior cerebral arteries, electrocardiogram, blood pressure, respiration, and end-tidal gases, will be sampled simultaneously at 1000 Hz (ADInstruments) and steady-state values calculated. Peripheral chemoreflex sensitivity will be determined as the cardiorespiratory responses per change in oxygen saturation (SpO2%) to isocapnic hypoxia. Central chemoreflex sensitivity will be determined as the cardiorespiratory responses per change in end tidal carbon dioxide tension (PETCO2) to hyperoxic hypercapnia. Peripheral chemoreflex tonicity will be determined as the average of a single breath nadir for each of the four hyperoxic trials (ventilatory measures). For cardiovascular measures, 15s averages over the 1-minute hyperoxic exposure will be calculated, and a nadir 15s obtained. The average of the 15s nadir values for each of the four hyperoxic trials will be calculated. Responses will be compared between sedentary and regularly exercising cross-sectional participants, and pre- and post-exercise training in longitudinal participants.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2022
Actual
Date of last participant enrolment
Anticipated
30/04/2023
Actual
Date of last data collection
Anticipated
30/07/2023
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment outside Australia
Country [1] 24352 0
New Zealand
State/province [1] 24352 0
Auckland

Funding & Sponsors
Funding source category [1] 310163 0
University
Name [1] 310163 0
University of Auckland
Country [1] 310163 0
New Zealand
Funding source category [2] 310254 0
Charities/Societies/Foundations
Name [2] 310254 0
Lottery Health Research (Lottery Grants Board)
Country [2] 310254 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
85 Park Road, Grafton
Auckland 1010
Country
New Zealand
Secondary sponsor category [1] 311249 0
None
Name [1] 311249 0
Address [1] 311249 0
Country [1] 311249 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309852 0
HDEC Extra Meeting Subcommittee
Ethics committee address [1] 309852 0
Ethics committee country [1] 309852 0
New Zealand
Date submitted for ethics approval [1] 309852 0
17/11/2021
Approval date [1] 309852 0
09/12/2021
Ethics approval number [1] 309852 0
2021 EXP 11418

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

Contacts
Principal investigator
Name 115610 0
Miss Thalia Babbage
Address 115610 0
Faculty of Medical and Health Sciences Department of Physiology
University of Auckland
85 Park Road
Grafton Auckland 1023
Country 115610 0
New Zealand
Phone 115610 0
+64277468230
Fax 115610 0
Email 115610 0
[email protected]
Contact person for public queries
Name 115611 0
Thalia Babbage
Address 115611 0
Faculty of Medical and Health Sciences Department of Physiology
University of Auckland
85 Park Road
Grafton Auckland 1023
Country 115611 0
New Zealand
Phone 115611 0
+64277468230
Fax 115611 0
Email 115611 0
[email protected]
Contact person for scientific queries
Name 115612 0
Thalia Babbage
Address 115612 0
Faculty of Medical and Health Sciences Department of Physiology
University of Auckland
85 Park Road
Grafton Auckland 1023
Country 115612 0
New Zealand
Phone 115612 0
+64277468230
Fax 115612 0
Email 115612 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.