Peripheral Vascular Effects of Sulfhydryl-containing Antihypertensive Pharmacotherapy on Microvascular Function and Vessel Remodeling in Hypertensive Humans

STUDY3224

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.

2016-07-20

2022-08-31

2022-12-31

Terminated

Early phase I

10

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.)

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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.', 'primaryPurpose': 'BASIC_SCIENCE', 'maskingInfo': {'masking': 'DOUBLE', 'maskingDescription': 'Investigator and Outcomes Assessor are masked according to treatment.', 'whoMasked': ['INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 10, 'type': 'ACTUAL'}}

2024-02-28