ENAC Blockade and Arterial Stiffness

Phase 2

Active, not recruiting

• Conditions: Overweight and Obesity; Insulin Resistance
• Interventions: Drug: Amiloride Pill; Drug: Placebo - Cap

• Registration Number: NCT03837626
• Lead Sponsor: University of Missouri-Columbia

Brief Summary

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.

Detailed Description

Overweight/obese males, pre- and post-menopausal females with insulin resistance, 30-70 years of age will be recruited. Following screening, eligible men and women will be randomly assigned to either amiloride (max dose 5mg) or placebo in a double-blinded design manner.

After randomization, subjects will be scheduled for an outpatient visit to the undergo baseline assessment of arterial stiffness (carotid femoral pulse wave velocity - cfPWV) and endothelial function (brachial popliteal artery flow mediated dilation). Subject assessment will be repeated at 12 weeks and at 24 weeks.

Study Timeline

• Study First Submitted: 2019-02-08
• Study First Submitted QC: 2019-02-08
• Study First Posted: 2019-02-12
• Study Start: 2019-07-15
• Primary Completion: 2024-10-05
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-05-01
• Study Completion: 2025-08-28

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 157

Inclusion Criteria

• 30 to 70 years of age at randomization
• Body mass index (BMI) 25.1-50 kg/m2 or waist circumference > 88 cm (> 35 in) in women and >102 cm (>40 in) in men. 3, 4
• One other characteristic of metabolic syndrome (elevated triglycerides ≥150 mg/dl; HDL cholesterol <40 mg/dl in men and <50 mg/dl in women; blood pressure ≥130/85 mm Hg or treatment for hypertension; impaired fasting glucose (≥100 mg/dl)) or fasting insulin level >10 mU/L (correlates with insulin resistance).

Exclusion Criteria

1. History of type 1 or type 2 diabetes
2. Known cardiovascular events within the last 12 months (stroke, acute coronary event, revascularization, heart failure hospitalization).
3. History of uncontrolled thyroid disease, chronic liver disease (cirrhosis) or GFR <50 ml/min.
4. Use of potassium sparing medications (angiotensin II receptor blockers, angiotensin converting enzymes inhibitors or mineralocorticoid receptor blockers) or use of potassium supplements.
5. Active cancer (This criterion does not apply to those subjects with basal cell carcinoma or stage 1 squamous cell carcinoma of the skin)
6. Excessive alcohol consumption (>14 drinks/week for men, >7 drinks/week for women)
7. Current tobacco use
8. Non controlled hypertension
9. Participation in regular exercise > 3 days/wk per week at a moderate or vigorous intensity
10. Pregnancy or lactation in women (or women not using contraceptives)
11. Women who plan to become pregnant during the duration of the trial
12. Chronic use of NSAIDs
13. Potassium level > 5.0 mqE/L at time of screening
14. Blood pressure at screening <110/70

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Amiloride	Amiloride Pill	6 months of amiloride (max dose 5 mg) treatment
Placebo	Placebo - Cap	6 months of daily placebo

Primary Outcome Measures

Name	Time	Method
Carotid femoral PWV	Baseline, 3 months (interim) and 6 months (final)	It is the gold standard non-invasive index of arterial stiffness. Transit time between carotid and femoral pressure waves is calculated using the foot-to-foot method. cfPWV is calculated as distance traveled by the pulse wave (i.e., femoral location-sternal notch minus sternal notch-carotid location) divided by pulse transit time. All the measurements will be done by the same blinded technician.The goal is to assess changes from baseline when compared to interim and final time point.

Secondary Outcome Measures

Name	Time	Method
Brachial artery flow mediated dilation (FMD)	Baseline, 3 months (interim) and 6 months (final)	The goal is to assess changes from baseline when compared to interim and final time point. \] Brachial artery FMD will be assessed at baseline and at 12-wk. FMD is a measurement of conduit artery endothelial function. FMD is assessed immediately after each PWV measurement. Shear rate AUC until peak diameter is calculated as stimulus for FMD and used in covariate analysis as described. All measurements will be performed, under co-I supervision by the same blinded technician.
Popliteal artery flow mediated dilation (FMD)	Baseline, 3 months (interim) and 6 months (final)	The goal is to assess changes from baseline when compared to interim and final time point. \] Popliteal artery FMD will be assessed at baseline and at 12-wk. FMD is a measurement of conduit artery endothelial function. FMD is assessed immediately after each PWV measurement. Shear rate AUC until peak diameter is calculated as stimulus for FMD and used in covariate analysis as described. All measurements will be performed, under co-I supervision by the same blinded technician.

Trial Locations

Locations (1)

University of Missouri Hospital and Clinics; 🇺🇸 Columbia, Missouri, United States