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

NCT07396857 | Recruiting

• 1 other identifier: 2025-7915
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Cardiovascular

Keywords

Arterial function; Sedentary time; Sex differences; Vasoactive substances

Outcome Measures

Primary Outcomes (3)

• Popliteal Low-Flow Mediated Constriction

  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

  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

  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 Outcomes (12)

• Carotid Artery Blood Flow Velocity

  Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.

• Middle Cerebral Artery Velocity

  Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.

• Popliteal Flow Mediated Dilation (FMD)

  Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.

• Physical Activity Behaviour Questionnaire

  At time of study enrolment

• Heart Rate Variability (HRV)

  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.

Study Arms (2)

Males

EXPERIMENTAL

Drug: Placebo; Drug: Fluconazole 150 mg

Females

EXPERIMENTAL

Drug: Placebo; Drug: Fluconazole 150 mg

Interventions

Fluconazole 150 mg DRUG

Participants will take 150mg of fluconazole, an EDHF inhibitor before and after a bout of prolonged sitting.

Females; Males

Placebo DRUG

Participants will take a placebo sugar pill before and after a bout of prolonged sitting as a control session.

Females; Males

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Dalhousie University: collaborator

Study Sites (1)

Dalhousie University

Halifax, Nova Scotia, B3H4R2, Canada

RECRUITING

Related Publications (18)

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MeSH Terms

Conditions

Sedentary Behavior

Interventions

Fluconazole

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Myles W O'Brien, PhD

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Molly K Courish, MSc, PhD(s)

CONTACT

902-818-0783; molly.courish@dal.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 2, 2026
• First Posted: February 9, 2026
• Study Start: November 1, 2025
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)