Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001767190
Ethics application status
Approved
Date submitted
22/10/2019
Date registered
12/12/2019
Date last updated
24/03/2022
Date data sharing statement initially provided
12/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Interactions between central and peripheral respiration's control cells in humans with high blood pressure.
Scientific title
Chemoreflex testing to assess interactions between central and peripheral chemoreflexes in human hypertension.
Secondary ID [1] 299777 0
None
Universal Trial Number (UTN)
U1111-1236-4527
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension 314878 0
Condition category
Condition code
Respiratory 313228 313228 0 0
Normal development and function of the respiratory system
Cardiovascular 313229 313229 0 0
Hypertension

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

All the following measurements and tests described will be conducted by a trained human physiologist staff member.

At an initial visit to the laboratory, written informed consent will be obtained from participants who will then undergo screening and familiarization. Anthropometric (height, weight, hip-to-waist ratio), demographic, clinical history information will be obtained, and health questionnaires and 7-day physical activity recall data will be collected.

Participants will then attend a single experimental session lasting ~3 hours, including set-up time. Experimental sessions 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.

At the experimental session, participants will be asked to lie in a semi-recumbent position on a medical examination couch and to remain in that position throughout the session. Bilateral internal carotid and vertebral artery blood flow will be measured using duplex Doppler ultrasound. This ultrasound examination is similar to scan done for pregnant women, but a large artery is examined. This is a simple and safe procedure and involves a probe being put on the patients’ skin over the region of interest with the help of a ‘water jelly’.

Participants will then be instrumented for continuous monitoring of BP, heart rate (HR), respiration, brachial artery blood flow and sympathetic nerve activity. More specifically, brachial BP will be measured with a clinically validated automated sphygmomanometer (Omron), using a cuff wrapped around the upper arm. In addition, beat-to-beat BP will be measured using finger photoplethysmography, using a small lightweight cuff wrapped around the finger. Heart rate will be measured using standard electrocardiogram involving the placement of several sticky patch electrodes on the collarbones and chest (standard 3 lead ECG). For breathing monitoring, participants will wear a mouthpiece/noseclip or oronasal mask (Hans Rudolph) and chest movements will be monitored with a belt placed around the thorax. Sympathetic nerve activity will be measured using the microneurgraphy technique. This involves the insertion of a small, sterile wire (unipolar tungsten microelectrodes, tip measuring 1-5 um) near the fibular head on the outside of the leg, to obtain a multiunit recording of postganglionic muscle sympathetic nerve activity from the peroneal nerve.

After a resting baseline of 20 min (last 5 min used for analysis), chemoreflex testing will be undertaken. Chemoreflex testing will involve five tests. Each test lasts 5 min and is separated by 15 min rest period. Each participant will receive all five tests in a randomised order. Each test involve the breathing of a different gas mixture, while the participant wears a mouthpiece/noseclip or oronasal mask. The five tests are: 1) hypercapnic hyperoxia (to evaluate central chemoreflex stimulation with diminished peripheral chemoreflex stimulation, using a gas concentration of: 7% CO2, 50% O2 and 43% N2); 2) isocapnic hypoxia (to evaluate peripheral chemoreflex stimulation, using a gas concentration of: 10% O2 and 90% N2); 3) hypercapnic hypoxia (to evaluate combined central and peripheral chemoreflex stimulation, using a gas concentration of: 7% CO2, 10% O2 and 83% N2); 4) isocapnic hyperoxia (to evaluate potential central effects of hyperoxia, using a gas concentration of: 50% O2 and 50% N2); and 5) hypocapnic hyperoxia (to evaluate central chemoreflex tonicity, using a gas concentration of: 50% O2 and 50% N2 which will be conducted with a rebreathing test).
Intervention code [1] 315849 0
Early detection / Screening
Comparator / control treatment
The "control" treatment are protocols 4) and 5) described above (i.e., isocapnic hyperoxia test and hypocapnic hyperoxia test) for intra-individual comparison. Also, the normotensive controls will be consider as "controls" for the inter-individual comparison.
Control group
Active

Outcomes
Primary outcome [1] 321725 0
Muscle sympathetic nerve activity as assessed by microneurography.
Timepoint [1] 321725 0
: Assessed at multiple timepoints during a single experimental session: hypercapnic hyperoxia (primary timepoint), isocapnic hypoxia, hypercapnic hypoxia, isocapnic hyperoxia and hypocapnic hyperoxia
Secondary outcome [1] 376012 0
Blood pressure as assessed by finger photoplethysmography.
Timepoint [1] 376012 0
Assessed at multiple timepoints during a single experimental session: hypercapnic hyperoxia, isocapnic hypoxia, hypercapnic hypoxia, isocapnic hyperoxia and hypocapnic hyperoxia

Eligibility
Key inclusion criteria
- Patients with essential hypertension (Stage 2, treated controlled or uncontrolled; office SBP greater than 140 mmHg or DBP greater than 90 mmHg);
- Normotensive controls (office SBP less than 120 mmHg and DBP less than 80 mmHg);
- BMI less than 35 kg.m2.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Significant arrhythmias (e.g., atrial fibrillation, previous VT / significant ventricular ectopy)
• Significant valvular heart disease
• Previous coronary artery bypass surgery
• Primary angioplasty for acute ST elevation
• Myocardial infarction
• Severe left ventricular dysfunction
• Recent (< 3 months) ischemic stroke
• Current smoker
• Body mass index < 18 kg/m2.
• Current pregnancy
• Users of recreational drugs
• Abusers of alcohol
• 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 active treatment for cancer
• Connective tissue or inflammatory disease
• Neurological disease
• Infection or pyrexial illness
• Uncontrolled thyroid disorders
• Renal impairment (e.g., chronic kidney disease with creatinine clearance <29 ml/min)

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled 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)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Other
Other design features
Both groups (hypertensive and normotensive subjects) will receive all 5 gas inhalation protocols in random order during the study.
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
For the assessment of normality and homogeneity of distribution of each variable will be performed using the Kolmogorov-Smirnov and Levene’s tests, respectively. Chi-square (X2) test will be used to analyse categorical data. Comparisons between groups and between trials will performed repeated measures ANOVA with appropriate post hoc tests.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
16/12/2019
Actual
2/03/2020
Date of last participant enrolment
Anticipated
17/05/2022
Actual
Date of last data collection
Anticipated
31/05/2022
Actual
Sample size
Target
30
Accrual to date
21
Final
Recruitment outside Australia
Country [1] 21936 0
New Zealand
State/province [1] 21936 0
Auckland

Funding & Sponsors
Funding source category [1] 304076 0
Charities/Societies/Foundations
Name [1] 304076 0
Auckland Medical Research Foundation
Country [1] 304076 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Private Bag 92019
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 304273 0
None
Name [1] 304273 0
Address [1] 304273 0
Country [1] 304273 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304568 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 304568 0
Ethics committee country [1] 304568 0
New Zealand
Date submitted for ethics approval [1] 304568 0
Approval date [1] 304568 0
06/08/2019
Ethics approval number [1] 304568 0
19/NTB/125

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

Contacts
Principal investigator
Name 97414 0
A/Prof James P Fisher
Address 97414 0
Faculty of Medical and Health Sciences
Department of Physiology
University of Auckland
85 Park Road
Grafton
Auckland 1023
Country 97414 0
New Zealand
Phone 97414 0
+6493737599
Fax 97414 0
Email 97414 0
[email protected]
Contact person for public queries
Name 97415 0
James P Fisher
Address 97415 0
Faculty of Medical and Health Sciences
Department of Physiology
University of Auckland
85 Park Road
Grafton
Auckland 1023
Country 97415 0
New Zealand
Phone 97415 0
+6493737599
Fax 97415 0
Email 97415 0
[email protected]
Contact person for scientific queries
Name 97416 0
James P Fisher
Address 97416 0
Faculty of Medical and Health Sciences
Department of Physiology
University of Auckland
85 Park Road
Grafton
Auckland 1023
Country 97416 0
New Zealand
Phone 97416 0
+6493737599
Fax 97416 0
Email 97416 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
Current Study Results
No documents have been uploaded by study researchers.

Update to Study Results
Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseSex differences in the sympathetic neurocirculatory responses to chemoreflex activation.2022https://dx.doi.org/10.1113/JP282327
EmbaseCentral and peripheral chemoreflexes in humans with treated hypertension.2023https://dx.doi.org/10.1113/JP284249
N.B. These documents automatically identified may not have been verified by the study sponsor.