The Role of EDHFs on Blood Pressure Following a Bout of Prolonged Sitting

April 7, 2026 updated by: Myles William O'Brien, Université de Sherbrooke

The Role of Endothelial-Derived Hyperpolarization Factors on 24-hr Blood Pressure Regulation Following a Bout of Prolonged Sitting

Canadians spend most of their day in sedentary postures (i.e., sitting, lying, reclining). While the beneficial impacts of physical activity on the heart are well-established, less is known about the consequences during time spent in sedentary postures. Currently, we know that spending time in a bout of uninterrupted sitting disrupts blood pressure regulation. However, it is unknown if there are any 'carry over' effects following uninterrupted sitting bouts (i.e., over the next 24-hours). The release of chemicals from arteries controls how stiff or relaxed they are and is important for controlling blood pressure. This is especially true for arteries directly impacted by sitting (e.g., the popliteal artery behind the knee) and that send blood to the brain (e.g., the carotid artery). We have also established that endothelial-derived hyperpolarizing factors (EDHF, chemicals that relax the artery) are important for the relaxation of the artery the popliteal artery. However, we do not know if the effects of EDHFs on this artery are decreased during or after a bout of uninterrupted sitting. A bout of prolonged sitting also causes blood pressure and fluctuations in blood pressure to increase. Importantly, we reported that fluctuations in blood pressure caused by sitting are higher in young males versus females, but average blood pressure was higher among females. These findings suggest that sitting exerts sex differences in the control of blood pressure. Importantly, these effects were only demonstrated during the 2-hour bout of sitting. As such, it is unknown whether blood pressure is negatively impacted after prolonged sitting. The proposed study will determine the impact of EDHFs on blood pressure regulation following a 2-hour bout of prolonged sitting among a group of healthy males and females. Continuous heart rate (via electrocardiogram) and blood pressure (via finger cuff), as well as blood flow from the common carotid artery (in the neck), middle cerebral artery (in the brain) and popliteal artery (behind the knee) will be measured before and after sitting (via ultrasound). The ability of the popliteal artery to relax will be assessed using ultrasound following the release of a pressure cuff. Finally, 24-hour blood pressure and heart rate will be recorded after sitting using a monitor worn for 24-hours. The role of EDHFs will be investigated by comparing 1) baseline blood flow and blood pressure responses (no sitting), 2) blood pressure responses following a 2-hour bout of sitting, and 3) the blood pressure responses following a 2-hour bout of sitting while suppressing the release of EDHFs (via fluconazole ingestion).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

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Study Contact

Study Contact

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Study Locations

  • Canada
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H4R2
        • Recruiting
        • Dalhousie University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Are between the ages of 18-65.
  • Have a body mass index of <40kg/m2 (non-obese).
  • Have not smoked nicotine or marijuana-containing products most days of the week within the past 6 months.
  • Have not been diagnosed with a cardiovascular, cerebrovascular, respiratory, or metabolic disease.
  • Are normotensive.
  • Are not currently taking any medications for cardiovascular, metabolic, pulmonary, or neurological disorders, or taking sildenafil regularly.
  • Are not allergic to the adhesive used to secure the activPAL activity monitors.
  • Are not pregnant or breastfeeding.
  • Are not regularly taking any of the following: another anti-fungal, heartburn medications containing cisapride (e.g., Propulsid), depression medications containing amitriptyline (e.g., Elavil) or nortriptyline (e.g., Pamelor), erythromycin (antibiotic), lipid lower medications (i.e., statins), non-steroidal anti-inflammatory drugs (e.g., ibuprofen), or vitamin A supplements.

Exclusion Criteria:

  • o Younger than 18 years old. Individuals younger than 18 demonstrate more variable peak FMD responses and require multiple assessments to determine peak response.

    • Over the age of 65. There are age-related impacts on arterial function and the responses to sitting.
    • Body mass index of >40 kg/m2 (i.e., obese II category)(6-8).
    • Smoked nicotine or marijuana-containing products most days of the week within the past 6 months. Cardiovascular health for participants who smoke is poor compared to those who do not smoke, which will negatively impact our arterial function outcomes.
    • Have been diagnosed with a cardiovascular, cerebrovascular, respiratory, or metabolic disease. Such conditions impact our assessments of arterial health. The results of unhealthy participants are not of interest in this study.
    • Hypertension (seated resting systolic pressure >139 mmHg and/or diastolic pressure >89 mmHg). Hypertensive individuals have impairments in artery health, which will affect their baseline artery health measures.
    • Hypotensive (seated resting systolic pressure <90 mmHg and/or diastolic pressure <60 mmHg). Hypotensive people are more likely to experience further reductions in blood pressure during the sitting protocol, which will increase the risk of fainting and/or dizziness.
    • Have a history of fainting and/or dizziness during sitting or standing.
    • Prescribed medications for cardiovascular, metabolic, pulmonary, or neurological disorders. This includes people using hormone replacement therapy. These medications will interfere with our assessments and interpretation of arterial health.
    • Have a known allergy to the clear medical adhesive used to secure the activPAL activity monitors.
    • Females who are pregnant or breastfeeding. Pregnant and breastfeeding females are ineligible to participate. This is due to the known increases in arterial vasodilation associated with pregnancy related sex hormones.
    • Currently or recently (within the past 6 months) regularly taking sildenafil or other medications that increase the relaxing effects of nitric oxide in arteries. Such medication will influence artery blood flow and flow-mediated dilation responses.
    • Are regularly taking any of the following: another anti-fungal, heartburn medications containing cisapride (e.g., Propulsid), depression medications containing amitriptyline (e.g., Elavil) or nortriptyline (e.g., Pamelor), erythromycin (antibiotic), lipid lower medications (i.e., statins), non-steroidal anti-inflammatory drugs (e.g., ibuprofen), or vitamin A supplements. These are to minimize the chance of a participant experiencing an adverse reaction to the fluconazole tablet.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Males
Drug: Placebo
Participants will take a placebo sugar pill before and after a bout of prolonged sitting as a control session.
Drug: Fluconazole 150 mg
Participants will take 150mg of fluconazole, an EDHF inhibitor before and after a bout of prolonged sitting.
Experimental: Females
Drug: Placebo
Participants will take a placebo sugar pill before and after a bout of prolonged sitting as a control session.
Drug: Fluconazole 150 mg
Participants will take 150mg of fluconazole, an EDHF inhibitor before and after a bout of prolonged sitting.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Popliteal Low-Flow Mediated Constriction
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting
During a period of distal cuff-induced ischemia, the endothelial-dependent vasoconstrictor response will be assessed via Duplex ultrasonography. The popliteal artery will be imaged slightly above the popliteal fossa. The L-FMC response will be quantified as the percent reduction in arterial diameter from baseline to the nadir diameter from the last 30-s of a 5-min distal cuff occlusion period.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting
Acute Blood Pressure
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Beat-by-beat systolic (SBP) and diastolic (DBP) blood pressure will be measured using finger photoplethysmography for 20 minutes before the bout of prolonged sitting, 20 minutes after 1-hour of sitting, and 20 minutes after 2-hours of sitting. Mean arterial pressure will be quantified as 1/3 SBP + 2/3 DBP.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Ambulatory Blood Pressure
Time Frame: This will be worn for a 24-hour period before the first prolonged sitting session, and for 24-hours after each bout of prolonged sitting.
Using an ABPMpro Ambulatory Blood Pressure Monitors, habitual blood pressure will be measured every 20-minutes during waking hours, and every 30-minutes during sleeping hours.
This will be worn for a 24-hour period before the first prolonged sitting session, and for 24-hours after each bout of prolonged sitting.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Carotid Artery Blood Flow Velocity
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Blood flow velocity will be measured immediately prior to the bifurcation in the common carotid artery using Duplex ultrasonography for 5 minutes.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Middle Cerebral Artery Velocity
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Blood flow velocity will be measured via transcranial Doppler over the trans-temporal window for 5 minutes.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Popliteal Flow Mediated Dilation (FMD)
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Following a period of distal cuff induced ischemia, the endothelial-dependent vasodilator response will be assessed via Duplex ultrasonography. The popliteal artery will be imaged slightly above the popliteal fossa. The FMD response will be quantified as the percent increase in arterial diameter from baseline to the peak diameter following the release of the distal cuff.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Physical Activity Behaviour Questionnaire
Time Frame: At time of study enrolment
A subjective questionnaire that provides information regarding habitual physical activity and sedentary behaviours.
At time of study enrolment
Heart Rate Variability (HRV)
Time Frame: Acute: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. Ambulatory: 24-hours at baseline, 24-hours after each bout of prolonged sitting.
Heart rate will be determined using cardiac intervals from a lead II electrocardiography during prolonged sitting, and from the built-in electrocardiogram in the ambulatory blood pressure monitor. HRV will be derived from these waveforms using an offline HRV analysis module. Time-domain (I.e., RMSSD), frequency-domain, low frequency (LF) power, high frequency (HF) power, and the LF/HF ratio will be quantified for each participant.
Acute: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. Ambulatory: 24-hours at baseline, 24-hours after each bout of prolonged sitting.
Carotid Intima Media Thickness (cIMT)
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
cIMT will be determined from a 5-minute recording of the carotid artery, imaged prior to the bifurcation using Duplex ultrasonography.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Carotid Artery Distensibility
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Distensibility will be determined from 5-minutes of recorded carotid artery imaging via Duplex ultrasonography, and will be calculated as the difference between average arterial diameter during systole and diastole.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Blood Pressure Varibility (BPV)
Time Frame: Acute: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. Ambulatory: 24-hours at baseline, 24-hours after each bout of prolonged sitting.
Beat-by-beat BPV during sitting will be quantified using the blood pressure measurements derived from finger photoplethysmography. This will be calculated as the average absolute difference between successive finger blood pressure measurements, for systolic blood pressure, diastolic blood pressure, and mean arterial pressure. Ambulatory BPV will be quantified from the 24-hour blood pressure monitors.
Acute: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. Ambulatory: 24-hours at baseline, 24-hours after each bout of prolonged sitting.
Cardiovagal Baroreflex Sensitivity (cvBRS)
Time Frame: Before prolonged sitting, after 1 hour of sitting, after 2-hours of sitting.
cvBRS will be quantified from beat-by-beat systolic blood pressure (SBP) and R-R intervals in a cvBRS software. cvBRS outcomes will be quantified from a minimum of 3 sequences in which beat-by-beat SBP changes were ≥1 mmHg and changes in R-R interval were ≥ 1 ms. Overall cvBRS is represented by the average slope of SBP and R-R interval regressions for the pooled sequences, and reported separately for both up and down sequences. Baroreflex effectiveness index (BEI) will be measured as the ratio of the number of SBP ramp-induced changes in RR interval to the total number of SBP ramps observed. This will be reported separately for both up and down sequences. This will be measured over a 20-minute time period.
Before prolonged sitting, after 1 hour of sitting, after 2-hours of sitting.
Baseline Arterial Diameters
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Arterial diameter of the popliteal and carotid arteries will be determined via Duplex ultrasonography over a minimum of 2-minutes.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Habitual Activity
Time Frame: Before first bout of sitting, after each bout of sitting.
Habitual activity will be measured using activPAL inclinometer-accelerometers positioned on the torso, thigh, and calf. Monitors will be waterproofed and attached 24-hr/day for 8 days via clear medical adhesive. Physical activity will be determined via validated, custom software that was developed and openly published by our group.
Before first bout of sitting, after each bout of sitting.
Habitual Postures
Time Frame: Before first bout of sitting, after each bout of sitting.
Habitual postures will be measured using activPAL inclinometer-accelerometers positioned on the torso, thigh, and calf. Monitors will be waterproofed and attached 24-hr/day for 8 days via clear medical adhesive. Time spent in postures (e.g., sitting versus lying time) will be determined via validated, custom software that was developed and openly published by our group.
Before first bout of sitting, after each bout of sitting.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Université de Sherbrooke

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Dalhousie University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Myles W O'Brien, PhD, Université de Sherbrooke

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

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Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 15, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 15, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 2, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 2, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 9, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2025-7915

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD will not be shared to maintain privacy and confidentiality of the participants.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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