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ENAC Blockade and Arterial Stiffness

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ClinicalTrials.gov Identifier: NCT03837626
Recruitment Status : Recruiting
First Posted : February 12, 2019
Last Update Posted : September 6, 2019
Sponsor:
Information provided by (Responsible Party):
Camila Manrique, 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.

Condition or disease Intervention/treatment Phase
Overweight and Obesity Insulin Resistance Drug: Placebo - Cap Drug: Amiloride Pill Phase 2 Phase 3

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 5 mg 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 artery flow mediated dilation ). Subject assessment will be repeated at 12 weeks and at 24 weeks.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 157 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Estrogen Receptor Alpha Signaling in Endothelial Cells Exacerbates Arterial Stiffening Via Upregulation of ENaC in Insulin Resistant Females
Estimated Study Start Date : September 4, 2019
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
6 months of daily placebo
Drug: Placebo - Cap
6 months of 1 pill a day

Experimental: Amiloride
6 months of amiloride 5 mg treatment
Drug: Amiloride Pill
5 mg day for 6 months




Primary Outcome Measures :
  1. Carotid femoral PWV [ Time Frame: 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 :
  1. Brachial artery flow mediated dilation (FMD) [ Time Frame: 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.



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Ages Eligible for Study:   30 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 30 to 70 years of age at randomization
  • Body mass index (BMI) 25.1-40 kg/m2 (weight stable during the prior 6 months)2 or waist circumference > 88 cm (> 35 in) in women and >102 cm (>40 in) in men. 3, 4
  • Pre-diabetes (fasting blood glucose 100-125 mg/dl or between 140-200 mg/dL 2 hours after OGTT glucose load).
  • Fasting insulin level >10 U/mL (correlates with insulin resistance).

Exclusion Criteria:

  1. Known cardiovascular disease (CVD), unstable angina, abnormal thyroid tests or liver disease, renal disease (GFR <60 ml/min)
  2. Use of diuretics, potassium sparing medications (angiotensin II receptor blockers. Angiotensin converting enzymes inhibitors or mineralocorticoid receptor blockers) or use of potassium supplements.
  3. Active cancer
  4. Autoimmune diseases
  5. Excessive alcohol consumption (>14 drinks/week for men, >7 drinks/week for women)
  6. Current tobacco use
  7. Body weight change ≥10% within the last 6 months
  8. Non controlled hypertension
  9. Surgical history for weight loss or use of weight-loss medications or active dieting
  10. Participation in exercise > 3 days/wk per week at a moderate or vigorous intensity
  11. Pregnancy or lactation in women (or women not using contraceptives)
  12. Women who plan to become pregnant during the duration of the trial
  13. Chronic use of NSAIDs
  14. Potassium level > 5.0 mqE/L at time of screening
  15. Blood pressure at screening <110/70

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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03837626


Contacts
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Contact: Camila Manrique Acevedo, MD 573-8820999 manriquec@health.missouri.edu

Locations
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United States, Missouri
University of Missouri Hospital and Clinics Recruiting
Columbia, Missouri, United States, 65201
Contact: Camila Manrique    573-882-2273    manriquec@health.missouri.edu   
Sponsors and Collaborators
University of Missouri-Columbia
Investigators
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Principal Investigator: Camila Manrique Acevedo, MD University of Missouri-Columbia

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Responsible Party: Camila Manrique, Associate Professor, Endocrinology, University of Missouri-Columbia
ClinicalTrials.gov Identifier: NCT03837626     History of Changes
Other Study ID Numbers: 2012990
First Posted: February 12, 2019    Key Record Dates
Last Update Posted: September 6, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Insulin Resistance
Overweight
Body Weight
Signs and Symptoms
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Amiloride
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Acid Sensing Ion Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Epithelial Sodium Channel Blockers
Diuretics, Potassium Sparing