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

157 Participants Needed

Trial Summary

What is the purpose of this trial?

To determine whether treatment with the ENaC inhibitor, amiloride, improves endothelial function and arterial stiffness in obese insulin resistant subjects in a randomized placebo-controlled trial examining pre and postmenopausal women and age-matched men.

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.

What data supports the effectiveness of the drug Amiloride for arterial stiffness in obesity?

The research suggests that weight loss, which can be achieved through various methods including certain medications, improves arterial stiffness, a condition linked to obesity. While Amiloride specifically isn't mentioned, the general improvement in arterial compliance with weight loss supports the potential benefit of treatments targeting obesity-related vascular issues. ^{1 2 3 4 5}

Is Amiloride safe for humans?

There is no specific safety data on Amiloride in the provided research articles, but it has been used in various treatments and is generally considered safe when prescribed by a doctor. ^{1 2 6 7 8}

How is the drug Amiloride unique for treating arterial stiffness in obesity?

Amiloride is unique because it is primarily a diuretic (a drug that helps remove excess fluid from the body) and is being explored for its potential to reduce arterial stiffness in obesity, a novel use compared to traditional treatments like lifestyle changes or other blood pressure medications. ^{1 9 10 11 12}

Research Team

Camila Manrique Acevedo, MD

Principal Investigator

University of Missouri-Columbia

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Effect of weight loss induced by energy restriction on measures of arterial compliance: A systematic review and meta-analysis. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Divergent effects of angiotensin-converting enzyme inhibition on blood pressure and endothelial function in obese humans. [2015]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Differential effects of renin-angiotensin-aldosterone system inhibition, sympathoinhibition and diuretic therapy on endothelial function and blood pressure in obesity-related hypertension: a double-blind, placebo-controlled cross-over trial. [2013]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Obesity and arterial compliance alterations. [2022]

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

Evidence of changes in alpha-1/AT1 receptor function generated by diet-induced obesity. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Overweightness, obesity and arterial stiffness in healthy subjects: a systematic review and meta-analysis of literature studies. [2018]

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

Short-term sibutramine therapy is associated with weight loss and improved endothelial function in obese patients with coronary artery disease. [2016]

8. China pubmed.ncbi.nlm.nih.gov

[Effects of life style intervention on obesity-related vascular dysfunction in children]. [2015]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Irbesartan improves arterial compliance more than lisinopril. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Different degree of intervention in 6-month weight-loss support and arterial stiffness: Secondary analysis of a randomized controlled trial. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Weight loss induced by nutritional and exercise intervention decreases arterial stiffness in obese subjects. [2022]

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

Arterial stiffness, lifestyle intervention and a low-calorie diet in morbidly obese patients-a nonrandomized clinical trial. [2021]