HealthyPhase 4NCT05176379
Endothelial Derived Hyperpolarization Factor and Vascular Control
A Phase 4 study testing Fluconazole 150 mg in people with Healthy, run by University of Oklahoma at 1 site in United States.
Trial summary
Most cardiometabolic diseases are characterized by increased muscle sympathetic nerve activity (MSNA) during rest and exercise which contributes to poor health outcomes. In healthy humans during muscle contraction, there is a blunting of skeletal muscle vascular responsiveness to increases in MSNA. Read more about this study
- Who is it for?
- Ages 18 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Fluconazole 150 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Feb 2022to May 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Normotensive (systolic blood pressure < 130 mmHg and/or diastolic blood pressure < 85 mmHg) individuals
- Individuals free of cardiovascular disease and metabolic disease
- Individuals free of any form of autonomic dysfunction
- Individuals with a BMI under 30 kg/m²
- Women that are premenopausal with a regular menstrual cycle (26-30 days)
Who cannot join
- Smokers, tobacco users (regular use in the last 6 months)
- Individuals with a blood pressure greater than 130/85
- Subjects who use Amiodarone, Sulphaphenazole
- Subjects who use S-warfarin, Tolbutamine, Phenytoin, Lonafarnib
- Cardiometabolic medication use (e.g. anti-hypertensives, insulin-sensitizing, statins)
- Sex hormone replacement medical use (e.g. testosterone, estrogen, progesterone)
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Department of Health and Exercise Science
Norman, Oklahoma, 73019
Michael Bemben, PhD, 405-325-5211, mgbemben@ou.edu
Jeremy M Kellawan, PhD, (405) 325-9028, kellawan@ou.edu
About this study
Official title: Endothelial Derived Hyperpolarization Factor and Regulation of Cerebral and Muscle Blood Flow
Most cardiometabolic diseases are characterized by increased muscle sympathetic nerve activity (MSNA) during rest and exercise which contributes to poor health outcomes. In healthy humans during muscle contraction, there is a blunting of skeletal muscle vascular responsiveness to increases in MSNA. However, the exact mechanisms involved are unknown although, best evidence suggests that the mechanism is endothelium derived, but nitric oxide (NO) and prostaglandin (PG) independent. Endothelium-derived hyperpolarizing factor (EDHF) is a NO and PG independent vasodilator in both cerebral and skeletal muscle circulations, however, it is unknown if EDHF contributes to vascular responsiveness during elevated MSNA. The application of lower body negative pressure (LBNP) is a safe and non-invasive manipulation that can be used to increase MSNA causing vasoconstriction in humans. Therefore, the purpose of this experiment is to determine if acute inhibition of EDHF alters central and peripheral vascular responses to LBNP at rest and during dynamic exercise. Thereby, providing evidence by which EDHF contributes to vascular control in healthy humans and identify it's potential as a therapeutic target for cardiometabolic diseases that are characterized by elevated MSNA
Read the detailed description
The purpose of this study is to investigate the importance of the endothelium-derived hyperpolarizing factor (EDHF) in regulation of muscle and brain blood flow during rest, sympathetic activation via lower body negative pressure (LBNP), and during rhythmic exercise. We hypothesize that acute inhibition of EDHF will blunt cardiovascular responses and decrease peripheral tissue oxygenation (specifically in the brain and muscle) in response to LBNP during rest and during exercise. This work will provide evidence that EDHF counter acts sympathetic nervous activity in healthy humans, thereby highlighting EDHF as a potentially crucial mechanism in human vascular control. Ultimately this work will provide basic knowledge need to open longer treatment windows and potentially novel therapies for cardiovascular complications from cardiometabolic diseases.
To test these hypotheses, we will complete two specific aims:
- To test the hypothesis whether EDHF inhibition alters sympathetic restraint muscle vasculature (termed, sympatholysis), we will compare changes in oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), Cardiac Output (CO) and Mean Arterial Pressure (MAP), Total Peripheral Resistance (TPR), Tissue Oxygen Saturation Index (TSI) during sympathetic activation (LBNP) and Handgrip exercise in two conditions: placebo vs. acute EDHF inhibition (Fluconazole).
II) To test the hypothesis whether EDHF inhibition alters regulation of cerebral blood flow during rest and sympathetic activation (LBNP), we will compare changes in cerebral vascular conductance index (CVCi), cerebral TSI as well as gain, coherence, and phase in transfer functional analysis during the exposure to Lower Body Negative Pressure (LBNP) in two conditions: placebo vs. acute EDHF inhibition (Fluconazole)
- Conditions
- Healthy
- Being tested
- Fluconazole 150 mg
- Keywords
- brain blood flow, muscle blood flow, endothelial function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluconazole 150 mgDrug
Also called placebo
A single acute 150 mg dose
| Study group | Role | What they receive |
|---|---|---|
| fluconazole | Experimental | fluconazole tablet/pill 150 mg, single acute dose Receives: Drug: Fluconazole 150 mg |
| Placebo | Placebo comparator | 250 mg pill microcrystalline Cellulose, single acute dose Receives: Drug: Fluconazole 150 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Near-Infrared Spectroscopy
Concentrations of Oxygen, deoxy, and Total Hemoglobin (micro molar)
Measured: up to 4 hours
Transcranial Doppler Ultrasound
middle cerebral artery blood velocity
Measured: up to 4 hours
Secondary outcomes (2)
Wireless electrocardiogram
heart rate
Measured: up to 4 hours
Finger photoplethysmography
Mean Arterial Pressure
Measured: up to 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2022
- Study start19 Feb 2022
- Primary completionDec 2024 (estimated)
- Study completionMay 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, single-blind, Placebo controlled, crossover design
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oklahoma
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeremy M Kellawan, PhD, Principal investigator, University of Oklahoma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05176379
- Sponsor's protocol ID
- 14056
- Status last verified
- Jul 2024
- First submitted
- 1 Dec 2021
- Last updated
- 23 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: We do not plan to share individual participant data
Publications
Matney JE, Buelow AA, Mixon C, Skillett SM, Ashley JD, Song J, Akbari Fakhrabadi A, Pointer P, Sprick JD, Black CD, Pereira HM, Kellawan JM. The effects of CYP450 inhibition on cerebrovascular control during rest and mild hypovolemia: An exploratory study in young, healthy adults. Physiol Rep. 2025 Dec;13(24):e70712. doi: 10.14814/phy2.70712.
PubMed 41420405
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endothelial Derived Hyperpolarization Factor and Regulation of Cerebral and Muscle Blood Flow
- ClinicalTrials.gov ID
- NCT05176379
- Acronym / sponsor ID
- 14056
- Conditions
- Healthy
- Keywords
- brain blood flow, muscle blood flow, endothelial function
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of OklahomaUniversity, hospital or other
- Study start
- 19 Feb 2022 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- May 2025 (estimated)
- First posted
- 4 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Most cardiometabolic diseases are characterized by increased muscle sympathetic nerve activity (MSNA) during rest and exercise which contributes to poor health outcomes. In healthy humans during muscle contraction, there is a blunting of skeletal muscle vascular responsiveness to increases in MSNA. However, the exact mechanisms involved are unknown although, best evidence suggests that the mechanism is endothelium derived, but nitric oxide (NO) and prostaglandin (PG) independent. Endothelium-derived hyperpolarizing factor (EDHF) is a NO and PG independent vasodilator in both cerebral and skeletal muscle circulations, however, it is unknown if EDHF contributes to vascular responsiveness during elevated MSNA. The application of lower body negative pressure (LBNP) is a safe and non-invasive manipulation that can be used to increase MSNA causing vasoconstriction in humans. Therefore, the purpose of this experiment is to determine if acute inhibition of EDHF alters central and peripheral vascular responses to LBNP at rest and during dynamic exercise. Thereby, providing evidence by which EDHF contributes to vascular control in healthy humans and identify it's potential as a therapeutic target for cardiometabolic diseases that are characterized by elevated MSNA
Detailed description
The purpose of this study is to investigate the importance of the endothelium-derived hyperpolarizing factor (EDHF) in regulation of muscle and brain blood flow during rest, sympathetic activation via lower body negative pressure (LBNP), and during rhythmic exercise. We hypothesize that acute inhibition of EDHF will blunt cardiovascular responses and decrease peripheral tissue oxygenation (specifically in the brain and muscle) in response to LBNP during rest and during exercise. This work will provide evidence that EDHF counter acts sympathetic nervous activity in healthy humans, thereby highlighting EDHF as a potentially crucial mechanism in human vascular control. Ultimately this work will provide basic knowledge need to open longer treatment windows and potentially novel therapies for cardiovascular complications from cardiometabolic diseases.
To test these hypotheses, we will complete two specific aims:
- To test the hypothesis whether EDHF inhibition alters sympathetic restraint muscle vasculature (termed, sympatholysis), we will compare changes in oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), Cardiac Output (CO) and Mean Arterial Pressure (MAP), Total Peripheral Resistance (TPR), Tissue Oxygen Saturation Index (TSI) during sympathetic activation (LBNP) and Handgrip exercise in two conditions: placebo vs. acute EDHF inhibition (Fluconazole).
II) To test the hypothesis whether EDHF inhibition alters regulation of cerebral blood flow during rest and sympathetic activation (LBNP), we will compare changes in cerebral vascular conductance index (CVCi), cerebral TSI as well as gain, coherence, and phase in transfer functional analysis during the exposure to Lower Body Negative Pressure (LBNP) in two conditions: placebo vs. acute EDHF inhibition (Fluconazole)
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Randomized, single-blind, Placebo controlled, crossover design
| Arm | Type | Receives |
|---|---|---|
| fluconazole | Experimental | Drug: Fluconazole 150 mgfluconazole tablet/pill 150 mg, single acute dose |
| Placebo | Placebo comparator | Drug: Fluconazole 150 mg250 mg pill microcrystalline Cellulose, single acute dose |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Normotensive (systolic blood pressure < 130 mmHg and/or diastolic blood pressure < 85 mmHg) individuals
- Individuals free of cardiovascular disease and metabolic disease
- Individuals free of any form of autonomic dysfunction
- Individuals with a BMI under 30 kg/m²
- Women that are premenopausal with a regular menstrual cycle (26-30 days)
Key exclusion criteria (7 listed)
- Smokers, tobacco users (regular use in the last 6 months)
- Individuals with a blood pressure greater than 130/85
- Subjects who use Amiodarone, Sulphaphenazole
- Subjects who use S-warfarin, Tolbutamine, Phenytoin, Lonafarnib
- Cardiometabolic medication use (e.g. anti-hypertensives, insulin-sensitizing, statins)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fluconazole 150 mgAlso: placeboA single acute 150 mg dose | Drug | Placebo, fluconazole |
Primary outcome
Near-Infrared Spectroscopy
Time frame: up to 4 hours
Concentrations of Oxygen, deoxy, and Total Hemoglobin (micro molar)
Transcranial Doppler Ultrasound
Time frame: up to 4 hours
middle cerebral artery blood velocity
2 secondary outcomes
Wireless electrocardiogram
Time frame: up to 4 hours
Finger photoplethysmography
Time frame: up to 4 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2024.
- Derived from this study: PubMed 41420405Matney JE, Buelow AA, Mixon C, Skillett SM, Ashley JD, Song J, Akbari Fakhrabadi A, Pointer P, Sprick JD, Black CD, Pereira HM, Kellawan JM. The effects of CYP450 inhibition on cerebrovascular control during rest and mild hypovolemia: An exploratory study in young, healthy adults. Physiol Rep. 2025 Dec;13(24):e70712. doi: 10.14814/phy2.70712.
- Individual participant dataSharing planned: No. We do not plan to share individual participant data
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeremy M Kellawan, PhD principal investigator
University of Oklahoma
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fluconazole 150 mg in people with Healthy, run by University of Oklahoma at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jeremy M Kellawan, PhD (4053259028, kellawan@ou.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Near-Infrared Spectroscopy (time frame: up to 4 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05176379, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2024.