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

NCT06287580 | Completed Early Phase 1 FDA Drug

• 1 other identifier: STU-2024-0140
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Older Adults; Essential Hypertension

Keywords

antihypertensive drug; cerebral blood flow; cognitive function

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

Antihypertensive drug treatment Arm

ACTIVE COMPARATOR

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

Placebo treatment Arm

PLACEBO COMPARATOR

Participants will receive placebo treatment for one to two weeks, with study visits for laboratory assessment at before and after intervention.

Other: Placebo

Interventions

chlorthalidone DRUG

chlorthalidone, 12.5 mg or 25 mg orally once daily

Antihypertensive drug treatment Arm

Placebo OTHER

Placebo tablet taken orally once daily

Placebo treatment Arm

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

Institute for Exercise and Environmental Medicine

Dallas, Texas, 75231, United States

Location

MeSH Terms

Conditions

Essential Hypertension

Interventions

Chlorthalidone

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Benzophenones; Phthalimides; Imides; Ketones; Sulfones; Sulfur Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• TAKURO WASHIO, Ph.D.

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Post Doctoral Research Fellow- Internal Medicine

Study Record Dates

• First Submitted: February 23, 2024
• First Posted: March 1, 2024
• Study Start: August 15, 2024
• Primary Completion: February 20, 2026
• Study Completion: February 20, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)