Amiloride for Arterial Stiffness in Obesity

Overseen By Camila Manrique Acevedo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of Missouri-Columbia

Must not be taking: Potassium sparing, NSAIDs

Disqualifiers: Diabetes, Cardiovascular events, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug amiloride can improve blood vessel function and reduce artery stiffness in individuals who are obese and insulin resistant. Participants will take either the amiloride treatment or a placebo (a harmless pill with no active drug) for six months. Suitable candidates include adults with a high BMI or large waist and at least one sign of metabolic syndrome, such as high blood pressure or cholesterol issues. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking potassium-sparing medications like certain blood pressure drugs and potassium supplements. If you're on these, you would need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that amiloride is generally safe for use. One study found that taking 10 mg to 20 mg of amiloride was as effective as another common blood pressure medicine and did not cause unwanted side effects. Another study discovered that even a very low dose of amiloride improved blood vessel function in mice without altering their blood pressure. These findings suggest that amiloride might be effective without causing major issues. While this information is encouraging, consider your own health and consult your doctor before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

Unlike the standard treatments for arterial stiffness in obesity, which often rely on lifestyle changes and medications like antihypertensives, amiloride offers a novel approach. Amiloride is unique because it targets sodium channels in the body, potentially reducing arterial stiffness by directly affecting fluid balance and blood pressure. Researchers are excited about amiloride because it could provide a more direct and efficient way to manage arterial stiffness, especially in individuals with obesity, who often face complex treatment challenges.

What evidence suggests that amiloride might be an effective treatment for arterial stiffness in obesity?

This trial will compare the effects of Amiloride with a placebo on arterial stiffness in individuals with obesity. Research has shown that amiloride can reduce arterial stiffness and improve blood vessel health. In one study, taking 10 mg of amiloride daily for four weeks lowered blood pressure and reduced artery stiffness, as measured by pulse wave velocity. Another study found that amiloride decreased blood vessel stiffness in female mice on a high-fat diet. These findings suggest that amiloride might enhance artery health in people with obesity and insulin resistance. ^{1 2 5 6 7}

Who Is on the Research Team?

Camila Manrique Acevedo, MD

Principal Investigator

University of Missouri-Columbia

Are You a Good Fit for This Trial?

This trial is for obese or overweight adults aged 30-70 with a BMI of 25.1-50 kg/m2 or certain waist measurements, plus one other metabolic syndrome feature like high triglycerides. It's not for smokers, heavy drinkers, those on specific heart/kidney medications, diabetics, very active individuals, pregnant/breastfeeding women, and people with recent severe health issues.

Inclusion Criteria

I am between 30 and 70 years old.

Your body mass index (BMI) is between 25.1 and 50, or your waist size is over 88 cm (35 inches) if you're a woman, or over 102 cm (40 inches) if you're a man.

You have high triglycerides, low "good" cholesterol, high blood pressure, or high blood sugar levels.

Exclusion Criteria

You currently smoke or use tobacco.

I regularly take NSAIDs for pain or inflammation.

I am not pregnant, breastfeeding, or if I am a woman capable of becoming pregnant, I am using contraception.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either amiloride or placebo for 6 months in a double-blinded design

24 weeks

3 visits (in-person) at baseline, 12 weeks, and 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Amiloride
• Placebo

Trial Overview

The study tests if amiloride (an ENaC blocker) can improve blood vessel function and reduce artery stiffness in obese insulin-resistant subjects compared to a placebo. The participants are pre/postmenopausal women and age-matched men who will be randomly assigned to the treatments.

How Is the Trial Designed?

Group I: Amiloride Experimental Treatment 1 Intervention

6 months of amiloride (max dose 5 mg) treatment

Group II: Placebo Placebo Group 1 Intervention

6 months of daily placebo

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

Approved in United States as Midamor for:

• Hypertension
• Congestive heart failure
• Edema due to cirrhosis of the liver

Approved in European Union as Amiloride for:

• Hypertension
• Congestive heart failure
• Ascites due to cirrhosis of the liver

Approved in Canada as Amiloride for:

• Hypertension
• Congestive heart failure
• Edema due to cirrhosis of the liver

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8031874/

Epithelial Sodium Channel Inhibition by Amiloride on Blood ...

Following 10 mg daily amiloride for 4 weeks, peripheral systolic BP (SBP), central SBP, and carotid‐radial pulse wave velocity were significantly reduced by − ...

2.

frontiersin.org

frontiersin.org/journals/physiology/articles/10.3389/fphys.2017.00456/full

Amiloride Improves Endothelial Function and Reduces ...

Ex vivo measurements of stiffness using atomic force microscopy showed that amiloride reduced endothelial stiffness in the aortae of female mice fed a WD by ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6319394/

Potential role of antihypertensive medications in preventing ...

The aim of this paper is to review the etiology of arterial stiffening and potential therapeutic approaches to modulate arterial fibrosis and stiffness.

4.

cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/26/NCT03837626/Prot_001.pdf

Estrogen receptor alpha signaling in endothelial cells exace

These data will aid in the understanding of how epithelial cell sodium channel (ENaC) contributes to the genesis of arterial stiffness in obese and insulin ...

5.

journals.physiology.org

journals.physiology.org/doi/10.1152/ajpheart.00155.2015

Regional variation in arterial stiffening and dysfunction in ...

Taken together, our data highlight important regional variations in the development of arterial stiffness and dysfunction associated with WD feeding.

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05228574?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AMILORIDE%20HYDROCHLORIDE))&rank=10

NCT05228574 | Treatment of Vascular Stiffness in ADPKD

A type of clinical study in which participants are identified as belonging to study groups and are assessed for biomedical or health outcomes. Participants may ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4728199/

a parallel-group, double-blind randomised phase 4 trial - PMC

At an adequate dose (10–20 mg), amiloride is as efficacious as 25–50 mg hydrochlorothiazide, and is not associated with undesirable metabolic consequences. The ...