Chlorthalidone for High Blood Pressure in Older Adults

Overseen By TAKURO WASHIO, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Hormonal therapy, others

Disqualifiers: Cardiovascular, Pulmonary, Diabetes, Alzheimer's, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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 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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those on three or more blood pressure medications. It's best to discuss your current medications with the trial team.

Is chlorthalidone safe for humans?

Chlorthalidone is generally considered safe for humans, with studies showing it can effectively lower blood pressure. A lower dose of 15 mg has fewer side effects, like less risk of low potassium levels, compared to the standard 25 mg dose. ^{1 2 3 4 5}

What makes the drug chlorthalidone unique for treating high blood pressure in older adults?

Chlorthalidone is unique because it is a thiazide-like diuretic with a longer half-life and wider distribution in the body compared to similar drugs, allowing for more effective blood pressure control and potential cardiovascular benefits. However, it may also carry a higher risk of side effects like hyponatremia (low sodium levels in the blood). ^{4 6 7 8 9}

What data supports the effectiveness of the drug Chlorthalidone for high blood pressure in older adults?

Research shows that Chlorthalidone, when combined with atenolol, significantly lowers blood pressure in patients with mild to moderate hypertension compared to a placebo. Additionally, its unique properties, such as a longer duration of action, make it an effective option for managing high blood pressure. ^{3 4 9 10 11}

Who Is on the Research Team?

TAKURO WASHIO, Ph.D.

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for older adults with high blood pressure who have not yet started treatment. Participants should be generally healthy, without conditions that could interfere with the study or pose additional risks.

Inclusion Criteria

I am between 60-85 years old with mild-to-moderate high blood pressure.

Exclusion Criteria

I have very high blood pressure or secondary hypertension.

Any history of substance abuse (other than tobacco)

Endurance-trained athletes

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either antihypertensive drug treatment or placebo for 2 weeks to assess brain blood flow, cognitive function, and nervous system control

2 weeks

2 visits (in-person) before and after intervention

Follow-up

Participants are monitored for changes in cognitive performance, muscle sympathetic nerve activity, and cerebral blood flow

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Chlorthalidone

Trial Overview The study tests if chlorthalidone (a drug for high blood pressure) affects brain blood flow and cognitive function compared to a placebo over two weeks. Researchers will monitor changes in participants' brain health and nervous system regulation.

How Is the Trial Designed?

Group I: Antihypertensive drug treatment Arm Active Control 1 Intervention

Participants will take a fixed dose of chlorthalidone (a diuretic, 25 mg orally once daily) for two week, with study visits for laboratory assessment at before and after intervention.

Group II: Placebo treatment Arm Placebo Group 1 Intervention

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

Chlorthalidone is already approved in United States, European Union for the following indications:

Approved in United States as Chlorthalidone for:

• Hypertension
• Edema caused by heart failure, renal failure, hepatic cirrhosis, estrogen therapy, and other conditions

Approved in European Union as Chlortalidone for:

• Hypertension
• Edema

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

In a study of 29,873 older adults, chlorthalidone did not show a significant advantage over hydrochlorothiazide in reducing adverse cardiovascular events or deaths, with similar rates of these outcomes between the two medications.

However, patients taking chlorthalidone were significantly more likely to experience electrolyte imbalances, particularly hypokalemia, indicating a safety concern with its use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chlorthalidone versus hydrochlorothiazide for the treatment of hypertension in older adults: a population-based cohort study. Dhalla, IA., Gomes, T., Yao, Z., et al.[2014]

The combination of azilsartan medoxomil and chlorthalidone significantly reduces blood pressure more effectively than other combinations, such as olmesartan medoxomil/hydrochlorothiazide, in four randomized controlled trials involving hypertensive patients.

This combination treatment is generally well tolerated, with only minor increases in serum creatinine and no significant impact on potassium levels, making it a safe option for managing hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azilsartan medoxomil/chlorthalidone: a new fixed-dose combination antihypertensive. Pierini, D., Anderson, KV.[2017]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Chlorthalidone versus hydrochlorothiazide for the treatment of hypertension in older adults: a population-based cohort study. [2014]

2. United States pubmed.ncbi.nlm.nih.gov

Atenolol and chlorthalidone therapy for hypertension: a double-blind comparison. [2019]

3. Brazil pubmed.ncbi.nlm.nih.gov

[Hemodynamic effects of low doses of chlorthalidone in patients with mild systemic arterial hypertension]. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

In older adults with hypertension, chlorthalidone vs. hydrochlorothiazide did not reduce major CV events or deaths at 2.4 y. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Chlorthalidone - a renaissance in use? [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Azilsartan medoxomil/chlorthalidone: a new fixed-dose combination antihypertensive. [2017]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy and reduced metabolic side effects of a 15-mg chlorthalidone formulation in the treatment of mild hypertension. A multicenter study. [2019]

8. England pubmed.ncbi.nlm.nih.gov

A randomized trial of the efficacy and safety of azilsartan medoxomil combined with chlorthalidone. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Hemodynamic effects of cadralazine or chlorthalidone in verapamil-treated elderly hypertensives. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Cardioprotective Effect of Thiazide-Like Diuretics: A Meta-Analysis. [2015]

11. United States pubmed.ncbi.nlm.nih.gov

Risk of hyponatremia with diuretics: chlorthalidone versus hydrochlorothiazide. [2014]