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Trial registered on ANZCTR

Registration number
Ethics application status
Date submitted
Date registered
Date last updated
Date data sharing statement initially provided
Type of registration
Prospectively registered

Titles & IDs
Public title
Influence of Exercise Training on Chemoreflex Sensitivity in healthy adult humans.
Scientific title
Influence of aerobic or resistance exercise training compared with sedentary lifestyle on central and peripheral chemoreflexes in healthy adult humans.
Secondary ID [1] 302294 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular disease 319039 0
Condition category
Condition code
Cardiovascular 316995 316995 0 0
Coronary heart disease
Cardiovascular 316996 316996 0 0
Cardiovascular 316997 316997 0 0
Other cardiovascular diseases
Respiratory 317040 317040 0 0
Normal development and function of the respiratory system

Study type
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 under supervision of a trained human physiologist staff member. The laboratory where all assessments will take place is located at the Exercise Nutrition and Metabolism Laboratory, Department of Exercise Sciences, Newmarket Campus, University of Auckland.

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 any questions, and obtain written informed consent from the participant. Anthropometric (height, weight), demographic, general health, physical activity readiness (Get Active questionnaire) and physical activity information will be obtained. Participants will then perform a handgrip strength test to enable classification of participants by strength (resistance training assessment) and a graded maximal exercise test to categorise participants according to their aerobic capacity (endurance training assessment).

During the handgrip strength test participants will use their dominant hand to maximally squeeze the dynamometer, with the highest of three trials obtained as the final value. During the graded maximal exercise test, participants will be instrumented with a heart rate monitor, mouthpiece and headset attached to a two-way valve with a room air inlet and outlet to a hose connected to a metabolic cart gas analysis system. Participants will perform 5-minute warm up at a self-selected pace, followed by a 3-minute adjustment period to determine the participant’s optimal speed for the duration of the maximal exercise test. The selected speed will remain constant for the duration of the test, with the gradient of the motorized treadmill increasing by 1% every 1 minute, beginning at 0%.

The second visit will be an experimental session. This visit will be scheduled ~2-7 days after the initial familiarisation/screening visit, as appropriate. However, premenopausal women will be studied during the first five days of their menstrual cycle (early follicular phase) or during the placebo/no-hormone phase of oral contraceptive use, as appropriate. This visit will be 90 minutes duration.

At the experimental session, participants will be asked to sit in a comfortable armchair and remain in that position throughout the session. Participants will be instrumented for continuous monitoring of blood pressure, heart rate, respiration and brain 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 two breathing tests. Tests are separated by a 15 minute rest period. The first test 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. The second test is hyperoxic hypercapnia (CO2 rebreathing), used to evaluate central chemoreflex stimulation with diminished peripheral chemoreflex stimulation). The participant will then be coached using a metronome and 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.
Intervention code [1] 318580 0
Early detection / Screening
Comparator / control treatment
The participant group who are sedentary will be age and sex matched to act as a control against resistance or aerobically trained participants. Participants will all receive the same treatment, and will also act as their own controls versus baseline values.
Control group

Primary outcome [1] 325106 0
Peripheral chemoreflex sensitivity (i.e., cardiorespiratory responses to isocapnic hypoxia).
Timepoint [1] 325106 0
Peripheral chemoreflex sensitivity will be assessed once, during the isocapnic hypoxia breathing test.
Secondary outcome [1] 386858 0
Central chemoreflex sensitivity (i.e., cardiorespiratory responses to hypercapnic hyperoxia)
Timepoint [1] 386858 0
Central chemoreflex sensitivity will be assessed once, during the CO2 rebreathing test.

Key inclusion criteria
• Aged 18-45 years old
• Men and women
• Healthy, with no chronic medical conditions (able to pass a PAR-Q+ questionnaire)
• Classified as either;

Endurance trained (participating in 4 or more hours per week of either type of training, on two or more days per week, for a continuous period of >12 months AND VO2peak >60 mL/kg/min for males or >55 mL/kg/min for females);

Resistance trained (participating in 4 or more hours per week of resistance training, on two or more days per week, for a continuous period of >12 months AND hand grip strength >58 kg for males or >38 kg for females);

Untrained (not engaging in any regular physical activity AND VO2max <41 mL/kg/min for males and <35 mL/kg/min females)

Minimum age
18 Years
Maximum age
45 Years
Both males and females
Can healthy volunteers participate?
Key exclusion criteria
• BMI <18 kg/m2
• Current smoker
• Users of recreational drugs
• Abusers of alcohol
• Underlying medical conditions
• Current pregnancy

Study design
Purpose of the study
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 design features
All three groups (resistance trained, aerobic trained and untrained) will receive all interventions with isocapnic hypoxia performed first followed by CO2 rebreathing.
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
Sample size estimates are based on Somers et al. who observed that minute ventilation increased by 96% (SD = 66) during isocapnic hypoxia (10% O2-90% N2 with titrated CO2). Therefore, with a sample size of 25 per group (75 in total) at 80% power and 5% alpha (two sample t-test) and assuming a similar standard deviation in all groups (resistance trained endurance trained and untrained), the minimal detectable difference would be 53% between any two groups in the minute ventilation response.

Anthropometric (e.g., BMI) and demographic (e.g., age) information gathered during the familiarisation/screening visit will be quantified using descriptive statistics (mean, SD, Median, IQR) and graphical presentations (boxplots, histograms, scatter plots). Normal distribution will be evaluated with Shapiro-Wilk tests. Levene’s test will be used to determine equal variance. A one-way repeated measures ANOVA will be used to compare the influence of exercise training history (resistance, endurance or untrained) on chemoreflex sensitivity. The Kruskal-Wallis test will be used for non-normally distributed data. Statistical analysis will be conducted using SPSS (IBM Corp.,). Significance will be set at p<0.05. Normally distributed data will be presented as mean (SD) while non-normally distributed data will be presented as median (interquartile range).

Recruitment status
Not yet recruiting
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment outside Australia
Country [1] 22985 0
New Zealand
State/province [1] 22985 0

Funding & Sponsors
Funding source category [1] 306719 0
Name [1] 306719 0
University of Auckland
Address [1] 306719 0
Faculty of Medical and Health Sciences
85 Park Road
Auckland 1023
New Zealand
Country [1] 306719 0
New Zealand
Primary sponsor type
University of Auckland
Faculty of Medical and Health Sciences
85 Park Road
Auckland 1023
New Zealand
New Zealand
Secondary sponsor category [1] 307302 0
Name [1] 307302 0
Address [1] 307302 0
Country [1] 307302 0

Ethics approval
Ethics application status
Ethics committee name [1] 306889 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 306889 0
Ministry of Health
Health and Disability Ethics Committees
133 Molesworth Street
PO Box 5013
Wellington 6140
Ethics committee country [1] 306889 0
New Zealand
Date submitted for ethics approval [1] 306889 0
Approval date [1] 306889 0
Ethics approval number [1] 306889 0

Brief summary
Exercise training has broad benefits for cardiovascular health. Surprisingly, the mechanisms by which these benefits occur are not well understood. Approximately 40% of the reduction in cardiovascular risk following exercise training cannot be attributed to improvements in traditional risk factors (e.g., changes in blood lipids). The chemoreflex is a specialised reflex mechanism that responds to changes in blood gas concentrations, and heightened chemoreflex sensitivity has been identified in chronic cardiovascular disease conditions such as hypertension, heart failure and coronary heart disease. However, it is currently unclear whether the cardiovascular benefits of exercise training are related to a reduction in chemoreflex sensitivity. It is possible that the chemoreflex is implicated in the cardiovascular response to exercise training and this concept is supported by basic animal research, but data are lacking in human participants. The primary objective of this study is to understand whether exercise training status (i.e., endurance or resistance trained) alters peripheral and central chemoreflex sensitivity in young and healthy adults. We hypothesise that having a specific and extensive exercise training history is associated with normalised or attenuated chemoreceptor sensitivity.
Trial website
Trial related presentations / publications
Public notes

Principal investigator
Name 105358 0
Miss Thalia Babbage
Address 105358 0
Faculty of Medical and Health Sciences Department of Physiology
University of Auckland
85 Park Road
Grafton Auckland 1023
Country 105358 0
New Zealand
Phone 105358 0
+64 277468230
Fax 105358 0
Email 105358 0
Contact person for public queries
Name 105359 0
Miss Thalia Babbage
Address 105359 0
Faculty of Medical and Health Sciences Department of Physiology
University of Auckland
85 Park Road
Grafton Auckland 1023
Country 105359 0
New Zealand
Phone 105359 0
+64 277468230
Fax 105359 0
Email 105359 0
Contact person for scientific queries
Name 105360 0
Miss Thalia Babbage
Address 105360 0
Faculty of Medical and Health Sciences Department of Physiology
University of Auckland
85 Park Road
Grafton Auckland 1023
Country 105360 0
New Zealand
Phone 105360 0
+64 277468230
Fax 105360 0
Email 105360 0

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results