ENAC Blockade and Arterial Stiffness

NCT03837626 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2012990
• Study Type: interventional
• Target: 137
• Locations: 1 country
• Sites: 1

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.

Conditions

Overweight and Obesity; Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• Carotid Femoral Pulse Wave Velocity

  cfPWV is the gold standard of arterial stiffness. It was assessd during experimental visits, under the same conditions in a blinded manner

  baseline, 3 and 6 mo

Other Outcomes (3)

• Systolic Blood Pressure

  3 and 6 mo

• Brachial Artery Flow Mediated Dilation (FMD)

  Baseline, 3 months (interim) and 6 months (final)

• Popliteal Artery Flow Mediated Dilation (FMD)

  Baseline, 3 months (interim) and 6 months (final)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

6 months of daily placebo

Drug: Placebo - Cap

Amiloride

EXPERIMENTAL

6 months of amiloride (max dose 5 mg) treatment

Drug: Amiloride Pill

Interventions

Placebo - Cap DRUG

6 months of 1 pill a day

Placebo

Amiloride Pill DRUG

Max dose of 5 mg a day for 6 months

Amiloride

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

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

Sponsors & Collaborators

• University of Missouri-Columbia: lead

Study Sites (1)

University of Missouri Hospital and Clinics

Columbia, Missouri, 65201, United States

Location

MeSH Terms

Conditions

Overweight; Obesity; Insulin Resistance

Interventions

Amiloride

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Camila Manrique, MD
• Organization: University of Missouri

manriquec@missouri.edu

573-882-2554

Study Officials

• Camila Manrique Acevedo, MD

  University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Endocrinology

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: February 12, 2019
• Study Start: July 15, 2019
• Primary Completion: October 5, 2024
• Study Completion: April 30, 2025
• Last Updated: December 30, 2025
• Results First Posted: December 30, 2025

Record last verified: 2025-11

Locations

US (1)