Acute Equol Supplementation and Vascular Function in Women With and Without CKD
- Registration Number
- NCT06128278
- Lead Sponsor
- University of Colorado, Denver
- Brief Summary
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 proposed project aims to determine the acute effect (1-hour, 2-hours, and 3-hours post ingestion) of oral equol supplementation on vascular function in postmenopausal women with and without CKD.
- Detailed Description
Patients with chronic kidney disease (CKD) have a significantly higher risk of cardiovascular diseases (CVD). Indeed, CVD is the leading cause of death in these patients. A primary reason why CKD so greatly exacerbates CVD risk is that CKD accelerates vascular dysfunction, including endothelial dysfunction (i.e., reduced brachial artery flow-mediated dilation \[FMDBA\]) and increased arterial stiffness (i.e., reduced compliance of the large-elastic arteries such as carotid artery), mediated in part by oxidative stress and inflammation that subsequently reduce the bioavailability of nitric oxide (NO; a vasodilator). Given CKD affects 15% of the U.S. population and 13% of the global population, CKD and its associated CVD risk are major public health concerns.
Women with CKD commonly experience menstrual disturbances, amenorrhea, and/or early menopause. Impaired ovarian function is well-known to compromise vascular health and increase CVD risk even in healthy women. As such, the vasculature of women with CKD may be exposed to the detrimental effects of both CKD and impaired ovarian function, which is secondary to CKD and menopause. Thus, declining kidney function and reduced circulating levels of cardioprotective sex hormones, particularly estradiol (E2), are two interrelated factors that contribute to vascular dysfunction and elevated CVD risk in women with CKD.
The long-term use of hormone replacement therapy (HRT) in postmenopausal women is controversial due to studies reporting its adverse effects on cardiovascular risk and breast cancer, which resulted from the long-term use of HRT. Current guidelines reserve the use of HRT only for short-term treatment of menopausal symptoms (e.g., vasomotor), prevention of bone loss and fractures, hypoestrogenism caused by hypogonadism, surgical menopause, or primary ovarian insufficiency. In women with CKD, limited studies examined the effect of HRT. Given reduced vascular dysfunction (associated with reduced circulating E2 secondary to CKD and menopause) and high CVD risk in postmenopausal women with CKD, there is a strong need for the identification of alternative pharmacological compounds to HRT that can improve vascular function in this population.
Equol is a gut microbiota-derived secondary metabolite of soy isoflavone (i.e., daidzein) and is an estrogen receptor (ER) β agonist. Equol has been identified as a vasoactive nutraceutical and has been shown to benefit vascular function in preclinical studies and clinical studies including healthy subjects. Similar to E2, the beneficial effect of equol on vascular function appears to be in part mediated by its anti-inflammatory and anti-oxidative properties that subsequently increase NO production. However, whether equol improves vascular function in postmenopausal women with CKD is unknown.
The overall goal of the proposed 2-period, double-blind, randomized, placebo-controlled, crossover pilot study is to evaluate the acute effect (1-hour, 2-hours, and 3-hours post-ingestion) of equol supplementation on vascular function (i.e., FMDBA and carotid compliance) and circulating markers of oxidative stress and inflammation in postmenopausal women with and without stage 3-4 CKD. This pilot study will also provide an effect size for designing a future trial testing the chronic effect of equol on vascular function in women with stage 3-4 CKD.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 38
- 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).
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description (1) S-equol, (2) Placebo S-equol This is a randomized, placebo-controlled, crossover study. Participants in one arm will receive S-equol (one visit) and then placebo (the other visit). (1) Placebo, (2) S-equol S-equol This is a randomized, placebo-controlled, crossover study. Participants in one arm will receive placebo (one visit) and then S-equl (the other visit).
- Primary Outcome Measures
Name Time Method Change in Brachial Artery Flow-Mediated Dilation Baseline; 1-hour, 2-hours, and 3-hours post ingestion 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.
- Secondary Outcome Measures
Name Time Method Change in Carotid Femoral Pulse Wave Velocity Baseline; 2-hour post ingestion A transcutaneous custom tonometer \[Noninvasive Hemodynamics Workstation (NIHem), Cardiovascular Engineering Inc.\] will be used to non-invasively assess carotid femoral pulse wave velocity.
Change in oxidative stress markers Baseline; 1-hour, 2-hours, and 3-hours post ingestion 8-isoprostane
Change in inflammation markers Baseline; 1-hour, 2-hours, and 3-hours post ingestion interleukin-6, tumor necrosis factor-α
Change in S-equol concentrations Baseline; 1-hour, 2-hours, and 3-hours post ingestion Plasma S-equol levels
Trial Locations
- Locations (1)
University of Colorado Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States