ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

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Trial registered on ANZCTR

Registration number

ACTRN12620001121954

Ethics application status

Approved

Date submitted

20/08/2020

Date registered

29/10/2020

Date last updated

15/08/2023

Date data sharing statement initially provided

29/10/2020

Date results provided

15/08/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

Breathing control and vein function in hypertension

Scientific title

Peripheral chemoreflex regulation of sympathetic outflow and venous function using pyridoxine supplements in human hypertension

Secondary ID [1]

nil known

Universal Trial Number (UTN)

U1111-1248-3119

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Hypertension

Condition category

Condition code

Cardiovascular

Hypertension

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Daily oral pyridoxine supplement (5 mg·kg-1·day-1) will be taken in pill form for 4 weeks. Adherence of intervention will be confirmed with drug tablet return and laboratory tests.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Placebo (microcellulose) pill

Control group

Placebo

Outcomes

Primary outcome [1]

Breathing response to 5 min hypoxia (i.e., peripheral chemoreflex) will be assess using a heated pneumotach attached to a mouth piece. Participants will be exposed to a gas mixture containing 10% O2 in nitrogen during this assessment

Timepoint [1]

At baseline and at 4 weeks follow-up

Primary outcome [2]

Blood pressure control. Brachial blood pressure will be measured with a clinically validated automated sphygmomanometer (Omron), using a cuff wrapped around the upper arm. Beat-to-beat BP will be measured using finger photoplethysmography, using a small lightweight cuff wrapped around the finger.

Timepoint [2]

Baseline and at 4 week follow-up

Secondary outcome [1]

Venous compliance will be quantified using high-resolution Doppler ultrasound (uSmart 3300, Terason) coupled with automated edge detection and wall tracking of arterial images. Lower limb vein diameter will measured during progressive thigh cuff inflation and deflation

Timepoint [1]

Baseline and 4 week follow up

Secondary outcome [2]

Muscle sympathetic nerve activity (SNA), Muscle SNA will be measured using a small, sterile wire (unipolar tungsten microelectrodes, tip measuring 1-5 um) inserted near the fibular head on the outside of the leg using published techniques.

Timepoint [2]

Baseline Baseline and 4 week follow up

Eligibility

Key inclusion criteria

-Patients with essential hypertension (At least Stage 2 hypertension; untreated office SBP greater or equal to 140 mmHg or DBP greater or equal to 90 mmHg);
-Men and women;
-Aged over 18 years;
-Body mass index <35 kg/m2

Minimum age

18 Years

Maximum age

85 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

-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)
-Current smoker
-Body mass index <18 kg/m2.
-Current pregnancy
-Current user of recreational drugs
-Current abuser 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.

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)

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
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 4

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Stopped early

Data analysis

Data analysis is complete

Reason for early stopping/withdrawal

Lack of funding/staff/facilities

Date of first participant enrolment

Anticipated

2/03/2022

Actual

18/05/2022

Date of last participant enrolment

Anticipated

28/10/2022

Actual

22/02/2023

Date of last data collection

Anticipated

30/11/2022

Actual

10/03/2023

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Auckland

Address [1]

85 Park Road, Grafton
Auckland 1010

Country [1]

New Zealand

Primary sponsor type

University

Name

University of Auckland

Address

85 Park Road, Grafton
Auckland 1010

Country

New Zealand

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Northern A Health and Disability Ethics Committe

Ethics committee address [1]

133 Molesworth Street
Thorndon
Wellington 6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

Approval date [1]

01/06/2020

Ethics approval number [1]

20/NTA/29

Summary

Brief summary

High blood pressure (hypertension) affects one in three people, and remarkably ~50% of treated patients remain hypertensive. We need to better understand the mechanisms regulating blood pressure in hypertensive patients if new therapies are to be devised. 

Current treatments target the heart and arterial resistance, but the ‘forgotten’ venous circulation has been largely neglected. We hypothesize that high levels of sympathetic activity in hypertension result in profound constriction of the veins, and that ameliorating this may be an effective way to help control arterial pressure. 

Our extensive work in hypertensive animal models indicates that the carotid bodies develop tonicity and heightened reflex sensitivity due to excessive ATP bioavailability acting via purinergic (P2) receptors, which drive sympathetic outflows. We wish to determine whether a non-selective P2 receptor blocker reduces peripheral chemoreflex sensitivity, sympathetic activity, venous tone and blood pressure in humans with hypertension. 

This project will provide novel mechanistic insights into carotid chemoreflex regulation and the neural control of the venous circulation. Translating insights from our animal models of hypertension into the human setting will lay the groundwork for future studies, potentially leading to a paradigm shift in the future treatment of hypertension.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof James Fisher

Address

University of Auckland
85 Park Road, Grafton
Auckland 1023

Country

New Zealand

Phone

+640212968936

Fax

jp.fisher@auckland.ac.nz

Contact person for public queries

Name

Mickey Fan

Address

University of Auckland
85 Park Road, Grafton
Auckland 1023

Country

New Zealand

Phone

+640212968936

Fax

mickey.fan@auckland.ac.nz

Contact person for scientific queries

Name

James Fisher

Address

University of Auckland
85 Park Road, Grafton
Auckland 1023

Country

New Zealand

Phone

+640212968936

Fax

jp.fisher@auckland.ac.nz

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Basic de-identified participant characteristics, resting blood pressure values

When will data be available (start and end dates)?

start date: 01/10/2022
end date: 01/10/2024

Available to whom?

Researchers whom have directly requested

Available for what types of analyses?

meta-analysis

How or where can data be obtained?

Direct email contact (jp.fisher@auckland.ac.nz)

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
9347	Study protocol					380394-(Uploaded-01-10-2020-06-43-17)-Study-related document.docx
9348	Ethical approval					380394-(Uploaded-01-10-2020-06-43-17)-Study-related document.pdf

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.

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