Acute Equol Supplementation and Vascular Function in Women With and Without CKD

Study Overview
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Brief Summary
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The risk of cardiovascular disease (CVD) is significantly elevated in patients with chronic kidney disease (CKD). Notably, women with CKD commonly experience menstrual disturbances induced by CKD, which may contribute to impaired vascular function and elevated CVD risk. However, most of the literature in nephrology focuses on male patients, and studies on women's vascular health are limited. Establishing effective therapies for improving vascular function and reducing CVD risk in women with CKD is a high research priority of the NIH. Equol contributes to improvement in vascular function, mediated in part by its anti-oxidative and anti-inflammatory properties. However, there is no information on the effect of equol on vascular function in women with CKD. The goal of the proposed project is to determine the acute effect (1 hour after ingestion) of oral equol supplementation on vascular function in postmenopausal women with and without CKD.

Official Title
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Acute Equol Supplementation and Vascular Function in Postmenopausal Women With and Without CKD

Conditions
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Chronic Kidney Diseases

Intervention / Treatment
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* Drug: S-equol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal (50-69 y) women Women with CKD including stage 3-4 (eGFR 15-59 ml/min/1.73m2) determined by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation Women without CKD (eGFR >60 ml/min/1.73m2) must be healthy (free from hypertension, kidney disease, CVD, diabetes, and other chronic disease as assessed by self-report, medical history, and screening labs). Exclusion Criteria: Use of HRT or has used HRT for <6 months prior to enrollment Advanced CKD requiring dialysis History of kidney transplant Use of immunosuppressant medications (unless taking a stable dosage for a quiescent disease) Current tobacco or nicotine use or history of use in the last 12 months Antioxidant and/or omega-3 fatty acid use within the 2 weeks prior to testing Marijuana use within 2 weeks prior to testing Consumption of soy and soy-based products 3 days prior to testing Uncontrolled hypertension in CKD group (BP>140/90 mmHg) Atrial fibrillation Active infection or antibiotic therapy Hospitalization in the last month

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: (1) S-equol, (2) Placebo<br> | Drug: S-equol<br>* Oral supplementation of S-equol<br>|
| Experimental: (1) Placebo, (2) S-equol<br> | Drug: S-equol<br>* Oral supplementation of S-equol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Brachial Artery Flow-Mediated Dilation | Flow-mediated dilation of the brachial artery will be performed using ultrasonography and analyzed with a commercially available software package as percent change in diameter from baseline following reactive hyperemia. | Baseline; 1 hour post ingestion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Carotid Femoral Pulse Wave Velocity | A transcutaneous custom tonometer [Noninvasive Hemodynamics Workstation (NIHem), Cardiovascular Engineering Inc.] will be used to non-invasively assess carotid femoral pulse wave velocity. | Baseline; 1 hour post ingestion | 
| Change in oxidative stress markers | 8-isoprostane | Baseline; 1 hour post ingestion | 
| Change in inflammation markers | interleukin-6, tumor necrosis factor-α | Baseline; 1 hour post ingestion |