Hypertension,EssentialPhase 1/2H2SPharmNCT03179163
Peripheral Vascular Effects of Sulfhydryl-containing Antihypertensive Pharmacotherapy on Microvessels in Humans
A Phase 1/2 study testing Captopril Pill, Enalapril Pill and Hydrochlorothiazide in people with Hypertension,Essential, run by Penn State University at 1 site in United States.
Trial summary
High blood pressure can cause physical changes to the blood vessels of the body (remodeling). If a person who has high blood pressure also has a lot of blood vessel remodeling with their condition, they are more likely to have poor results with medical treatment for hypertension. Read more about this study
- Who is it for?
- Ages 40 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension,Essential
- What is being tested?
- Captopril Pill, Enalapril Pill and Hydrochlorothiazide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jul 2016to 31 Dec 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Women and men
- 40-65 years
- Blood pressure: Normotensive <120/80 mmHg Hypertensive ≥140/90 mmHg and <160/110 mmHg
- HbA1C of <6.5%
- Women are post-menopausal and not taking hormone replacement therapy, or have normal cycles and are tested in the early follicular phase
- Subjects may or may not be taking one doctor-prescribed drug to lower blood pressure (e.g. diuretic, ACE inhibitor).
- Must be able to stop physician-prescribed antihypertensive drug for the duration of the subject's participation in the study (with the approval of their personal physician).
Who cannot join
- Relevant to all subjects:
- current medications which could conceivably alter the cardiovascular or thermoregulatory control or responses (e.g. beta blockers, calcium channel blockers, ACE inhibitors, angiotensin receptor blockers)
- taking a diuretic (also see below)
- allergy to test substances
- allergy to latex
- nicotine use (smoking, chewing tobacco, etc.)
Show all 22Show fewer
- illegal/recreational drug use
- pregnancy or breastfeeding
- diabetes
- Relevant to hypertensive subjects only:
- contraindication for all three pharmacotherapy drugs used in this study
- o Note: Subjects who have a contraindication (e.g. a condition, medication with a known interaction, known allergy) to only one or two of the three pharmacotherapy drugs, may be assigned one of the pharmacotherapy drugs that is not contraindicated.
- history of having taken an ACE inhibitor with antioxidant properties (e.g. Captopril, Zofenopril)
- kidney problems
- liver problems
- history of heart disease or failure
- history of blood clots or stroke
- angioedema
- electrolyte imbalance
- planned surgery requiring general anesthesia during the pharmacotherapy period
- peripheral vascular disease
- diuretics (a subject taking only a diuretic to control the subject's hypertension may be included in the study if the subject stops taking the diuretic for the duration of the subject's participation in the study with the approval of the subject's personal physician.)
Trial locations and contacts
1 site in 1 country.
United States1 site
Pennsylvania State University
University Park, Pennsylvania, 16802
About this study
Official title: Peripheral Vascular Effects of Sulfhydryl-containing Antihypertensive Pharmacotherapy on Microvascular Function and Vessel Remodeling in Hypertensive Humans
High blood pressure can cause physical changes to the blood vessels of the body (remodeling). If a person who has high blood pressure also has a lot of blood vessel remodeling with their condition, they are more likely to have poor results with medical treatment for hypertension. The researchers examine the impact of different classes of drugs that doctors use to treat high blood pressure (hypertension) on blood vessel remodeling. Some drugs that doctors prescribe for their patients contain a "sulfhydryl group" (a sulfur atom bonded to a hydrogen atom). Drugs that have the sulfhydryl group may reduce blood vessel remodeling more that drugs that do not. For this study, participants who have high blood pressure perform the experiments, take a drug for 16-weeks to lower blood pressure, and repeat the experiments. The researchers randomly assign one of three drugs to participants who have high blood pressure: a diuretic ("water pill"), a drug containing a sulfhydryl (SH) group, or a drug that does not contain a sulfhydryl group. Participants who do not have high blood pressure perform the experiments, but do not take any of the drugs. In some of our experiments, the researchers use a technique called "microdialysis" (MD). With MD, the researchers perfuse some research drugs into the skin on the forearm through tiny tubing that mimics capillaries. These MD drugs mimic or block substances the body naturally makes to control the small blood vessels in the skin. The drugs remain in nickel-sized areas around the tubing and do not go into the rest of the body. The researchers also analyze very small skin samples (skin biopsy) obtained from the forearm. Lastly, the researchers use a standard technique called "flow mediated dilation" (FMD) that uses blood pressure cuffs and ultrasound to look at the health of larger blood vessels in the body. FMD includes placing a small tablet of nitroglycerin under the tongue during part of the test.
Read the detailed description
Upon initial screening and again within a week of testing, all subjects will have an assessment of 24-hour ambulatory blood pressure. Subject screening will be performed by the Penn State Clinical Translational Research Center (CTRC) medical staff and will include a physical exam by a clinician, anthropometry, and a chemical and lipid profile, liver and renal function. Women will be either postmenopausal (absence of menstruation of >1 year and Follicle Stimulating Hormone (FSH) >25 milli-international units per milliliter (mlU/ml)) and not be taking hormone replacement therapy, or normally menstruating and tested in the early follicular phase of their cycle. Subjects will also go through an assessment of conduit vessel endothelial and vascular smooth muscle function with brachial artery flow-mediated vasodilation (FMD), and sublingual nitroglycerin.
Subjects will undergo initial microdialysis experiments and biopsy samples will be obtained. Subjects will then be randomly assigned to treatment group. Blood pressure will be monitored every 2 weeks and weekly compliance checks will be made by the researcher's nurse coordinator. 24-hour ambulatory blood pressure monitoring will be conducted monthly to determine the efficacy of antihypertensive treatment and to inform dosing titration. Examining pharmacokinetic and dynamic data from the literature indicate that blood pressure lowing and peripheral vascular effects are maximized by 12 weeks of antihypertensive therapy and maintained thereafter. After 16 weeks of the assigned intervention, subjects will repeat microdialysis experiments and additional cutaneous biopsy samples will be obtained. Conduit artery measures including brachial artery FMD and responsiveness to sublingual nitroglycerin will also be evaluated at this time.
- Conditions
- Hypertension,Essential
- Being tested
- Captopril Pill, Enalapril Pill, Hydrochlorothiazide
- Keywords
- Hypertension, Blood Pressure, Cardiovascular Disease, Angiotensin Converting Enzyme (ACE) Inhibitor, Diuretic, Nitric Oxide, Hydrogen Sulfide, Captopril, Enalapril, Hydrochlorothiazide, Microcirculation, Skin
- Medical subject headings
- Essential Hypertension, Hypertension, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Captopril PillDrug
Also called National Drug Code (NDC) # 00781-8061-01
ACEi+SH
Enalapril PillDrug
Also called NDC# 51672-4039-03
ACEi
HydrochlorothiazideDrug
Also called NDC# 00603-3857-32
diuretic
| Study group | Role | What they receive |
|---|---|---|
| Normotensive | No intervention | Blood Pressure <120/80 mmHg |
| Hypertensive - ACE inhibitor with sulfahydrl donor (ACEi +SH) | Experimental | Captopril Pill intervention Blood Pressure ≥140/90 mmHg and <160/110 mmHg Receives: Drug: Captopril Pill |
| Hypertensive - ACE inhibitor (ACEi) | Experimental | Enalapril Pill intervention Blood Pressure ≥140/90 mmHg and <160/110 mmHg Receives: Drug: Enalapril Pill |
| Hypertensive - Diuretic | Active comparator | Hydrochlorothiazide intervention Blood Pressure ≥140/90 mmHg and <160/110 mmHg Receives: Drug: Hydrochlorothiazide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Endothelium Dependent Vasodilation
This measurement is performed using a laser Doppler flow meter. The flow meter produces a non-invasive qualitative and dimensionless index of blood flow in blood vessels during the localized perfusion of the endothelium-dependent vasodilatory acetycholine in a dose response fashion. The results are the differences in the area under the curve units=(laser Doppler flux/MAP)*logAch concentration
Measured: 16 weeks
Secondary outcomes (2)
Systolic Blood Pressure
Blood pressure is measured via brachial auscultation manually or with a critical care monitor. The peak blood pressure during a cardiac cycle when the heart contracts.
Measured: 16 Weeks
Diastolic Blood Pressure
Blood pressure is measured via brachial auscultation manually or with a critical care monitor. The lowest blood pressure during a cardiac cycle when the heart is between beats.
Measured: 16 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2017
- Study start20 Jul 2016
- Primary completion31 Aug 2022
- Study completion31 Dec 2022
Why it stopped: COVID shut down human subjects research and then the grant funding expired
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hypertension,EssentialStudies of the same condition, open and under way.
- More trials run by Penn State UniversityThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects are grouped as normal (\<120/80 mmHg) and hypertensive (≥140/90 mmHg and \<160/110 mmHg). All subjects undergo one round of experiments. Hypertensive subjects received randomly-assigned antihypertension medication angiotensin converting enzyme inhibitor with a sulfahydrl donor (ACEi+SH), angiotensin converting enzyme inhibitor (ACEi), or diuretic for 16 weeks and then repeat experiments. Normotensive subjects receive no intervention and repeat experiments16 weeks after initial experiments as a time control.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Penn State University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Lacy Alexander, Penn State University
- Investigators
- Lacy M Alexander, PhD, Principal investigator, Penn State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03179163
- Sponsor's protocol ID
- STUDY3224
- Other IDs
- 5R01HL093238, 120058
- Acronym
- H2SPharm
- Status last verified
- Feb 2024
- First submitted
- 2 Jun 2017
- Last updated
- 28 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Peripheral Vascular Effects of Sulfhydryl-containing Antihypertensive Pharmacotherapy on Microvascular Function and Vessel Remodeling in Hypertensive Humans
- ClinicalTrials.gov ID
- NCT03179163
- Acronym / sponsor ID
- H2SPharm / STUDY3224
- Conditions
- Hypertension,Essential
- Keywords
- Hypertension, Blood Pressure, Cardiovascular Disease, Angiotensin Converting Enzyme (ACE) Inhibitor, Diuretic, Nitric Oxide, Hydrogen Sulfide, Captopril
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: COVID shut down human subjects research and then the grant funding expired
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Penn State UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 20 Jul 2016 (actual)
- Primary completion
- 31 Aug 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 7 Jun 2017 (actual)
- Results
- Posted 28 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
High blood pressure can cause physical changes to the blood vessels of the body (remodeling). If a person who has high blood pressure also has a lot of blood vessel remodeling with their condition, they are more likely to have poor results with medical treatment for hypertension. The researchers examine the impact of different classes of drugs that doctors use to treat high blood pressure (hypertension) on blood vessel remodeling. Some drugs that doctors prescribe for their patients contain a "sulfhydryl group" (a sulfur atom bonded to a hydrogen atom). Drugs that have the sulfhydryl group may reduce blood vessel remodeling more that drugs that do not. For this study, participants who have high blood pressure perform the experiments, take a drug for 16-weeks to lower blood pressure, and repeat the experiments. The researchers randomly assign one of three drugs to participants who have high blood pressure: a diuretic ("water pill"), a drug containing a sulfhydryl (SH) group, or a drug that does not contain a sulfhydryl group. Participants who do not have high blood pressure perform the experiments, but do not take any of the drugs. In some of our experiments, the researchers use a technique called "microdialysis" (MD). With MD, the researchers perfuse some research drugs into the skin on the forearm through tiny tubing that mimics capillaries. These MD drugs mimic or block substances the body naturally makes to control the small blood vessels in the skin. The drugs remain in nickel-sized areas around the tubing and do not go into the rest of the body. The researchers also analyze very small skin samples (skin biopsy) obtained from the forearm. Lastly, the researchers use a standard technique called "flow mediated dilation" (FMD) that uses blood pressure cuffs and ultrasound to look at the health of larger blood vessels in the body. FMD includes placing a small tablet of nitroglycerin under the tongue during part of the test.
Detailed description
Upon initial screening and again within a week of testing, all subjects will have an assessment of 24-hour ambulatory blood pressure. Subject screening will be performed by the Penn State Clinical Translational Research Center (CTRC) medical staff and will include a physical exam by a clinician, anthropometry, and a chemical and lipid profile, liver and renal function. Women will be either postmenopausal (absence of menstruation of >1 year and Follicle Stimulating Hormone (FSH) >25 milli-international units per milliliter (mlU/ml)) and not be taking hormone replacement therapy, or normally menstruating and tested in the early follicular phase of their cycle. Subjects will also go through an assessment of conduit vessel endothelial and vascular smooth muscle function with brachial artery flow-mediated vasodilation (FMD), and sublingual nitroglycerin.
Subjects will undergo initial microdialysis experiments and biopsy samples will be obtained. Subjects will then be randomly assigned to treatment group. Blood pressure will be monitored every 2 weeks and weekly compliance checks will be made by the researcher's nurse coordinator. 24-hour ambulatory blood pressure monitoring will be conducted monthly to determine the efficacy of antihypertensive treatment and to inform dosing titration. Examining pharmacokinetic and dynamic data from the literature indicate that blood pressure lowing and peripheral vascular effects are maximized by 12 weeks of antihypertensive therapy and maintained thereafter. After 16 weeks of the assigned intervention, subjects will repeat microdialysis experiments and additional cutaneous biopsy samples will be obtained. Conduit artery measures including brachial artery FMD and responsiveness to sublingual nitroglycerin will also be evaluated at this time.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Subjects are grouped as normal (<120/80 mmHg) and hypertensive (≥140/90 mmHg and <160/110 mmHg). All subjects undergo one round of experiments. Hypertensive subjects received randomly-assigned antihypertension medication angiotensin converting enzyme inhibitor with a sulfahydrl donor (ACEi+SH), angiotensin converting enzyme inhibitor (ACEi), or diuretic for 16 weeks and then repeat experiments. Normotensive subjects receive no intervention and repeat experiments16 weeks after initial experiments as a time control.
| Arm | Type | Receives |
|---|---|---|
| Normotensive | No intervention | –Blood Pressure <120/80 mmHg |
| Hypertensive - ACE inhibitor with sulfahydrl donor (ACEi +SH) | Experimental | Drug: Captopril PillCaptopril Pill intervention Blood Pressure ≥140/90 mmHg and <160/110 mmHg |
| Hypertensive - ACE inhibitor (ACEi) | Experimental | Drug: Enalapril PillEnalapril Pill intervention Blood Pressure ≥140/90 mmHg and <160/110 mmHg |
| Hypertensive - Diuretic | Active comparator | Drug: HydrochlorothiazideHydrochlorothiazide intervention Blood Pressure ≥140/90 mmHg and <160/110 mmHg |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Women and men
- 40-65 years
- Blood pressure: Normotensive <120/80 mmHg Hypertensive ≥140/90 mmHg and <160/110 mmHg
- HbA1C of <6.5%
- Women are post-menopausal and not taking hormone replacement therapy, or have normal cycles and are tested in the early follicular phase
Key exclusion criteria (22 listed)
- current medications which could conceivably alter the cardiovascular or thermoregulatory control or responses (e.g. beta blockers, calcium channel blockers, ACE inhibitors, angiotensin receptor blockers)
- taking a diuretic (also see below)
- allergy to test substances
- allergy to latex
- nicotine use (smoking, chewing tobacco, etc.)
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 |
|---|---|---|
| Captopril PillAlso: National Drug Code (NDC) # 00781-8061-01ACEi+SH | Drug | Hypertensive - ACE inhibitor with sulfahydrl donor (ACEi +SH) |
| Enalapril PillAlso: NDC# 51672-4039-03ACEi | Drug | Hypertensive - ACE inhibitor (ACEi) |
| HydrochlorothiazideAlso: NDC# 00603-3857-32diuretic | Drug | Hypertensive - Diuretic |
Primary outcome
Change in Endothelium Dependent Vasodilation
Time frame: 16 weeks
This measurement is performed using a laser Doppler flow meter. The flow meter produces a non-invasive qualitative and dimensionless index of blood flow in blood vessels during the localized perfusion of the endothelium-dependent vasodilatory acetycholine in a dose response fashion. The results are the differences in the area under the curve units=(laser Doppler flux/MAP)*logAch concentration
2 secondary outcomes
Systolic Blood Pressure
Time frame: 16 Weeks
Diastolic Blood Pressure
Time frame: 16 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Hypertension,Essential
Recruiting
The Effect of Self-Acupressure on Blood Pressure, Stress, and Well-Being Levels in Individuals With Hypertension
PRIMARY HYPERTENSION
Active, not recruiting
Smartphone-Guided Paced Breathing and Aerobic Exercise for Essential Hypertension
Essential (Primary) Hypertension
Recruiting
Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension
Atherosclerosis Cardiovascular Disease
Not yet recruitingObservational study
A Study to Evaluate the Effectiveness and Safety of S-amlodipine-based Monotherapy and Combination Therapy
Hypertension (HTN), Hypertension
Recruiting
Community Health Worker Support to Lower Blood Pressure After a Pregnancy With High Blood Pressure
Pregnancy-Associated Hypertension, Gestational Hypertension
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.
Lacy M Alexander, PhD principal investigator
Penn State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Captopril Pill, Enalapril Pill and Hydrochlorothiazide in people with Hypertension,Essential, run by Penn State University 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 7 inclusion and 22 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: stopped early, as of the sponsor's last update on 28 Feb 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Endothelium Dependent Vasodilation (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Feb 2024.