Arterial Stiffness and Blood Pressure

NCT06495710 | Recruiting DMC

• 1 other identifier: CARB-007-23F
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 3

Brief Summary

Hypertension is a common and treatable disorder that remains the leading preventable cause of heart disease. Blood pressure treatment relies mainly on upper arm blood pressure readings and ignores blood vessel physiology and underlying individual genetic information. Older Veterans with hypertension are less likely to be treated to goal blood pressure because there are conflicting recommendations for what constitutes "optimal" in older adults. The investigators have developed a novel way to non-invasively assess the components of blood vessel stiffness that is related to blood pressure (load-dependent stiffness). This project will generate new knowledge about how different blood pressure treatment goals (intensive vs standard) impact different components of arterial stiffness and if these differences can be explained through genetic analysis. Results from this project will offer the VA an updated blueprint for personalizing blood pressure care in older adults, ultimately improving cardiovascular health.

Conditions

Hypertension; Vascular Stiffness; Aging

Keywords

hypertension; Vascular Stiffness; Aging

Outcome Measures

Primary Outcomes (2)

• Load-dependent arterial stiffness measured with pulse wave velocity (m/s)

  Load dependent stiffening is measured with ultrasound and tonometry and is the stiffness component due to elevated blood pressure increasing collagen fiber loading without an intrinsic change to the artery wall. The primary outcomes of load-dependent stiffness will be assessed at baseline and after 3, 6 and 12 months of guideline-based antihypertensive therapy.

  12 months

• Structural arterial stiffness measured with pulse wave velocity (m/s)

  Structural stiffening is measured with ultrasound and tonometry and is the stiffness component due to growth (eg. intima-media thickening) and remodeling (eg. elastin fragmentation, collagen accumulation) of the arterial wall. The primary outcomes of structural arterial stiffness will be assessed at baseline and after 3, 6 and 12 months of guideline-based antihypertensive therapy.

  12 months

Secondary Outcomes (2)

• Total arterial stiffness measured with pulse wave velocity (m/s)

  12 months

• Brachial blood pressure

  12 months

Other Outcomes (4)

• Safety outcome - Acute Kidney Injury

  12 months

• Safety outcome - Electrolyte abnormalities

  12 months

• Safety outcome - Hypotension

  12 months

Study Arms (2)

Intensive BP targets

EXPERIMENTAL

\<120 mmHg systolic)

Other: Blood pressure treatment algorithm

Standard blood pressure targets

ACTIVE COMPARATOR

\<140 mmHg systolic

Other: Blood pressure treatment algorithm

Interventions

Blood pressure treatment algorithm OTHER

Single or combination antihypertensive therapy as needed: 1) amlodipine (2.5-10 mg), 2) telmisartan (20-80 mg) or losartan (25-100 mg), 3) chlorthalidone (6.25-25 mg), or 4) spironolactone (12.5-50 mg). a two-drug regimen with either amlodipine + chlorthalidone or telmisartan + chlorthalidone will be initiated following randomization. If a diuretic is contraindicated, amlodipine + telmisartan will be initiated. For those over 75 years, either amlodipine or telmisartan will be initiated at baseline if SBP is \<140 mmHg. In the standard treatment group (SBP goal of \< 140 mmHg), participants will either be prescribed amlodipine or telmisartan/losartan as initial therapy. If \>3 medications are necessary to reach the intensive goal and no first line options remain, potassium sparing diuretics or direct vasodilators will be considered.

Intensive BP targets; Standard blood pressure targets

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants from VA VISN 7, 9, and 12 will be eligible to participate if they are over age 60 years and have a diagnosis of hypertension or take antihypertensive medications (up to 4).
• Veterans will require documented SBP readings on 2 or more office visits that are 140 mmHg or average home blood pressure readings 135 mmHg to be eligible for the trial.
• Participants must be willing to be randomized to intensive or standard blood pressure treatment and have blood pressure medications adjusted per the study protocol.
• They must be willing to undergo tonometric evaluation of arterial stiffness, and carotid artery ultrasound.

You may not qualify if:

• Participants who have an indication for a specific BP lowering medication that is not included in the study protocol or a known secondary cause of hypertension will be excluded.
• Patients will be excluded if they have:
• a standing SBP \<110 mmHg
• past history of a recent CVD event in the past 12 months (i.e., coronary artery disease event/intervention, congestive heart failure exacerbation or heart failure hospitalization, atrial fibrillation, or peripheral arterial disease intervention)
• a class I indication for betablocker use including atrial arrhythmias
• left-ventricular systolic function \<50%, \>moderate aortic stenosis
• history of stroke
• chronic kidney disease (eGFR\<30 mL/min/m2) or proteinuria in excess of 1 gram/day or polycystic kidney disease
• active cancer (other than untreated, non-metastatic prostate cancer and non-melanoma skin cancer)
• hypoxemic pulmonary disease
• active rheumatologic or connective tissue diseases (i.e., systemic lupus erythematosus, rheumatoid arthritis, etc.)
• human immunodeficiency virus
• illness with any infectious etiology or fever \>38°C (i.e., upper respiratory illness, gastrointestinal illness, etc.)
• hospitalization for any reason within the prior 4 weeks
• Participants will be excluded if arm circumference is too large/small to allow accurate blood pressure recordings

Sponsors & Collaborators

• VA Tennessee Valley Health Care System: collaborator
• Birmingham, Alabama VA Medical Center: collaborator
• The Lundquist Institute: collaborator
• University of Wisconsin, Madison: collaborator
• VA Office of Research and Development: lead

Study Sites (3)

Birmingham VA Medical Center, Birmingham, AL

Birmingham, Alabama, 35233-1927, United States

NOT YET RECRUITING

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Nashville, Tennessee, 37212-2637, United States

ENROLLING BY INVITATION

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, 53705-2254, United States

RECRUITING

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Adam Gepner

  William S. Middleton Memorial Veterans Hospital, Madison, WI

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adam Gepner

CONTACT

(608) 256-1901; adam.gepner@va.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2024
• First Posted: July 11, 2024
• Study Start: May 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)