ENAC Blockade and Arterial Stiffness

NCT ID: NCT03837626

Last Updated: 2025-12-30

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

137 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-15

Study Completion Date

2025-04-30

Brief Summary

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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

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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.

Conditions

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Overweight and Obesity Insulin Resistance

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Placebo

6 months of daily placebo

Group Type PLACEBO_COMPARATOR

Placebo - Cap

Intervention Type DRUG

6 months of 1 pill a day

Amiloride

6 months of amiloride (max dose 5 mg) treatment

Group Type EXPERIMENTAL

Amiloride Pill

Intervention Type DRUG

Max dose of 5 mg a day for 6 months

Interventions

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Placebo - Cap

6 months of 1 pill a day

Intervention Type DRUG

Amiloride Pill

Max dose of 5 mg a day for 6 months

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

30 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Missouri-Columbia

OTHER

Sponsor Role lead

Responsible Party

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Camila Manrique, MD

Associate Professor, Endocrinology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Camila Manrique Acevedo, MD

Role: PRINCIPAL_INVESTIGATOR

University of Missouri-Columbia

Locations

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University of Missouri Hospital and Clinics

Columbia, Missouri, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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2012990

Identifier Type: -

Identifier Source: org_study_id