Effects of Antihypertensive Drug Treatment on Brain Blood Flow, Cognition, and Regulation of Nervous System in Older Adults With Hypertension.

Antihypertensive Drug Effects on Cerebral Hemodynamics and Sympathetic Control in Older Hypertensive Patients

High blood pressure (BP) is a public health problem worldwide. Nearly three-quarters of older adults (age ~60 years) in the United States have high BP. High BP links to many health problems, like stroke. Drug treatments are typically used in clinics to reduce high BP and the risk of associated health problems. However, these drug treatments may not always benefit brain health. For example, drug treatment may reduce brain blood flow, which may reduce cognitive function in older adults with high BP. Alternatively, reduced brain blood flow may cause high BP due to increased nervous system activity (the so-called "fight or flight response"). Thus, monitoring brain blood flow may help to manage high BP during drug treatment.

It is unknown if brain blood flow and its control will be altered by drug treatment in older high BP patients. Therefore, study team will recruit older adults with high BP, who receive either drug treatment or a placebo for 1 to 2 weeks and will assess brain blood flow, cognitive function, and nervous system control before and after treatment.

Results from this study will provide novel and clinically relevant information on the impact of drug treatment for high BP on brain health. Investigators expect these results will suggest that it is crucial to measure brain blood flow, which may be a therapeutic new target for BP control and brain health.

Study Overview

• Status: Completed
• Conditions: Essential Hypertension; Older Adults
• Intervention / Treatment: Other: Placebo; Drug: chlorthalidone

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75231
      • Institute for Exercise and Environmental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Older men and women with prehypertension or mild-to-moderate essential hypertension (clinic systolic blood pressure 120-169 and/or diastolic blood pressure 80-109 mmHg).

Exclusion Criteria:

• Any evidence of cardiovascular or pulmonary disease by medical history or by physical examination
• Severe hypertension (systolic BP ≥170 and/or diastolic BP ≥110 mmHg; for safety reasons) or secondary hypertension
• Being on ≥3 antihypertensive agents
• Chronic kidney disease (an estimated glomerular filtration rate >45 mL/min) or renal failure
• Diabetes mellitus (fasting glucose ≥126 mg/dL or 2-hour oral glucose tolerance test, glucose level ≥200 mg/dL) or other systemic illness
• Any history of substance abuse (other than tobacco)
• Current cigarette smokers
• History of gouty arthritis
• Taking hormonal replacement therapy
• Endurance-trained athletes
• Diagnosed Alzheimer's disease and related dementias

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Antihypertensive drug treatment Arm; Participants will take a fixed dose of chlorthalidone (a diuretic, 12.5 mg or 25 mg orally once daily) for one to two week, with study visits for laboratory assessment at before and after intervention.	Drug: chlorthalidone; chlorthalidone, 12.5 mg or 25 mg orally once daily
Placebo Comparator: Placebo treatment Arm; Participants will receive placebo treatment for one to two weeks, with study visits for laboratory assessment at before and after intervention.	Other: Placebo; Placebo tablet taken orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Muscle sympathetic nerve activity (MSNA) from baseline at post intervention	Muscle sympathetic nerve activity will be measured using microneurography at the peroneal nerve. Muscle sympathetic nerve activity will be quantified by identification and measurement of sympathetic bursts in the integrated neurogram and expressed as burst frequency (mean number of bursts per unit time)	Baseline, post intervention
Change in cognitive performance from baseline at post intervention via Stroop Color and Word Test	Change in cognitive performance is measured by Stroop Color and Word Test. Accuracy and reaction time in the Stroop Color and Word test are computed to assess cognitive performance.	Baseline, post intervention
Change in Cerebral blood flow from baseline at post intervention	A probe will be placed over an artery in participant's neck and temple. Total cerebral blood flow is calculated as a sum of blood flow from the four arteries of the internal carotid artery and vertebral artery. The distribution of cardiac output to the brain is calculated as the percentage of total cerebral blood flow to cardiac output.	Baseline, post intervention

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: TAKURO WASHIO, Ph.D., University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2024
• Primary Completion (Actual): February 20, 2026
• Study Completion (Actual): February 20, 2026

Study Registration Dates

• First Submitted: February 23, 2024
• First Submitted That Met QC Criteria: February 23, 2024
• First Posted (Actual): March 1, 2024

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: cognitive function; cerebral blood flow; antihypertensive drug
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension; Essential Hypertension; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amides; Benzene Derivatives; Phthalimides; Isoindoles; Benzenesulfonamides; Sulfonamides; Sulfones; Ketones; Benzophenones; Imides; Chlorthalidone
• Other Study ID Numbers: STU-2024-0140

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No