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Peripheral Vascular Effects of Sulfhydryl-containing Antihypertensive Pharmacotherapy on Microvessels in Humans (H2SPharm)

Primary Purpose

Hypertension,Essential

Status
Enrolling by invitation
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Captopril Pill
Enalapril Pill
Hydrochlorothiazide
Sponsored by
Penn State University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Hypertension,Essential focused on measuring Hypertension, Blood Pressure, Cardiovascular Disease, ACE Inhibitor, Diuretic, Nitric Oxide, Hydrogen Sulfide, Captopril, Enalapril, Hydrochlorothiazide, Microcirculation, Skin

Eligibility Criteria

40 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • 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).

Exclusion Criteria:

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.)
  • 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.)

Sites / Locations

  • Pennsylvania State University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

No Intervention

Experimental

Experimental

Active Comparator

Arm Label

Normotensive

Hypertensive - ACEi +SH

Hypertensive - ACE inhibitor (ACEi)

Hypertensive - Diuretic

Arm Description

Blood Pressure <120/80 mmHg

Captopril Pill intervention Blood Pressure ≥140/90 mmHg and <160/110 mmHg

Enalapril Pill intervention Blood Pressure ≥140/90 mmHg and <160/110 mmHg

Hydrochlorothiazide intervention Blood Pressure ≥140/90 mmHg and <160/110 mmHg

Outcomes

Primary Outcome Measures

laser Doppler blood flow
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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
June 2, 2017
Last Updated
February 16, 2022
Sponsor
Penn State University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT03179163
Brief Title
Peripheral Vascular Effects of Sulfhydryl-containing Antihypertensive Pharmacotherapy on Microvessels in Humans
Acronym
H2SPharm
Official Title
Peripheral Vascular Effects of Sulfhydryl-containing Antihypertensive Pharmacotherapy on Microvascular Function and Vessel Remodeling in Hypertensive Humans
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Enrolling by invitation
Study Start Date
July 20, 2016 (Actual)
Primary Completion Date
August 31, 2022 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Penn State University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension,Essential
Keywords
Hypertension, Blood Pressure, Cardiovascular Disease, ACE Inhibitor, Diuretic, Nitric Oxide, Hydrogen Sulfide, Captopril, Enalapril, Hydrochlorothiazide, Microcirculation, Skin

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
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 (ACEi+SH, 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
InvestigatorOutcomes Assessor
Masking Description
Investigator and Outcomes Assessor are masked according to treatment.
Allocation
Randomized
Enrollment
46 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Normotensive
Arm Type
No Intervention
Arm Description
Blood Pressure <120/80 mmHg
Arm Title
Hypertensive - ACEi +SH
Arm Type
Experimental
Arm Description
Captopril Pill intervention Blood Pressure ≥140/90 mmHg and <160/110 mmHg
Arm Title
Hypertensive - ACE inhibitor (ACEi)
Arm Type
Experimental
Arm Description
Enalapril Pill intervention Blood Pressure ≥140/90 mmHg and <160/110 mmHg
Arm Title
Hypertensive - Diuretic
Arm Type
Active Comparator
Arm Description
Hydrochlorothiazide intervention Blood Pressure ≥140/90 mmHg and <160/110 mmHg
Intervention Type
Drug
Intervention Name(s)
Captopril Pill
Other Intervention Name(s)
National Drug Code (NDC) # 00781-8061-01
Intervention Description
ACEi+SH
Intervention Type
Drug
Intervention Name(s)
Enalapril Pill
Other Intervention Name(s)
NDC# 51672-4039-03
Intervention Description
ACEi
Intervention Type
Drug
Intervention Name(s)
Hydrochlorothiazide
Other Intervention Name(s)
NDC# 00603-3857-32
Intervention Description
diuretic
Primary Outcome Measure Information:
Title
laser Doppler blood flow
Description
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.
Time Frame
16 weeks
Secondary Outcome Measure Information:
Title
Systolic Blood Pressure
Description
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.
Time Frame
16 Weeks
Title
Diastolic Blood Pressure
Description
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.
Time Frame
16 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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). Exclusion Criteria: 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.) 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.)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lacy M Alexander, PhD
Organizational Affiliation
Penn State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pennsylvania State University
City
University Park
State/Province
Pennsylvania
ZIP/Postal Code
16802
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Peripheral Vascular Effects of Sulfhydryl-containing Antihypertensive Pharmacotherapy on Microvessels in Humans

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