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

NCT03179163 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: STUDY32245R01HL093238120058
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension,Essential

Keywords

Hypertension; Blood Pressure; Cardiovascular Disease; Angiotensin Converting Enzyme (ACE) Inhibitor; Diuretic; Nitric Oxide; Hydrogen Sulfide; Captopril; Enalapril; Hydrochlorothiazide; Microcirculation; Skin

Outcome Measures

Primary Outcomes (1)

• 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

  16 weeks

Secondary Outcomes (2)

• Systolic Blood Pressure

  16 Weeks

• Diastolic Blood Pressure

  16 Weeks

Study Arms (4)

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

Drug: Captopril Pill

Hypertensive - ACE inhibitor (ACEi)

EXPERIMENTAL

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

Drug: Enalapril Pill

Hypertensive - Diuretic

ACTIVE COMPARATOR

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

Drug: Hydrochlorothiazide

Interventions

Captopril Pill DRUG

ACEi+SH

Also known as: National Drug Code (NDC) # 00781-8061-01

Hypertensive - ACE inhibitor with sulfahydrl donor (ACEi +SH)

Enalapril Pill DRUG

ACEi

Also known as: NDC# 51672-4039-03

Hypertensive - ACE inhibitor (ACEi)

Hydrochlorothiazide DRUG

diuretic

Also known as: NDC# 00603-3857-32

Hypertensive - Diuretic

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women and men
• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Penn State University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Pennsylvania State University

University Park, Pennsylvania, 16802, United States

Location

MeSH Terms

Conditions

Essential Hypertension; Hypertension; Cardiovascular Diseases

Interventions

Captopril; Enalapril; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Vascular Diseases

Intervention Hierarchy (Ancestors)

Proline; Imino Acids; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Dipeptides; Oligopeptides; Peptides; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Lacy M. Alexander, Ph.D.
• Organization: Penn State

lma191@psu.edu

8148671781

Study Officials

• Lacy M Alexander, PhD

  Penn State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Investigator and Outcomes Assessor are masked according to treatment.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor Kinesiology

Model Details: 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.

Study Record Dates

• First Submitted: June 2, 2017
• First Posted: June 7, 2017
• Study Start: July 20, 2016
• Primary Completion: August 31, 2022
• Study Completion: December 31, 2022
• Last Updated: February 28, 2024
• Results First Posted: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)