Sex Hormone and Vascular Function in Women With CKD

Chronic Kidney Diseases Clinical Trial

Official title:

Sex Hormone and Vascular Function in Women With CKD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05471518
• Other study ID #: 21-3018
• Status: Recruiting
• Start date: July 1, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: November 2023
• Source: University of Colorado, Denver
• Contact: Ester S Oh, Ph.D.
• Phone: 303-724-3765
• Email: ester.oh[@]cuanschutz.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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 the field of nephrology focuses on male patients, and studies on women's vascular health are limited. Moreover, endogenous sex hormones, particularly estradiol, are well-documented to be cardioprotective in women without CKD; however, the role of sex hormones on vascular function in women with CKD remains unclear. The goals of the proposed project are: 1) to evaluate vasuclar function in pre- and post-menopausal women with CKD vs. age-matched healthy women; 2) to evaluate sex hormone concentrations and determine whether they associate with vascular function in the proposed cohort; and 3) to gain mechanistic insight on the association between sex hormones and vascular dysfunction in the proposed cohort.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Pre- (18-44 y) and post-menopausal (55-75 y) women

2. Individuals with CKD including stage 3-4 (eGFR 15-59 ml/min/1.73m2) determined by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation

3. Controls must be healthy (free from hypertension, kidney disease, cardiovascular disease, diabetes, and other chronic disease as assessed by self-report, medical history, and screening labs). Premenopausal healthy women must have a regular menstrual cycle (25-35 d).

Exclusion Criteria:

1. Perimenopausal (45-54 y) women

2. Pregnancy, lactation, or less than one year post-partum

3. Use of hormonal birth control methods, hormone replacement therapy, or a levonorgestrel intrauterine device (IUD) insertion for a duration less than 6 months

4. Advanced CKD requiring dialysis

5. History of kidney transplant

6. Use of immunosuppressant medications (unless taking a stable dosage for a quiescent disease in CKD group)

7. Antioxidant and/or omega-3 fatty acid use within the 2 weeks prior to testing

8. Current tobacco or nicotine use or history of use in the last 12 months

9. Marijuana use within 2 weeks prior to testing

10. Uncontrolled hypertension in CKD group (BP >140/90 mmHg)

11. Atrial fibrillation

12. Active infection or antibiotic therapy

13. Hospitalization in the last month

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Other:
• No intervention
No intervention

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Circulating/Urinary Markers of Antioxidant Status/Oxidative stress	Serum TAS, plasma/urinary 8-isoprostane, 8-OHdG will be measured using ELISA.	Baseline
Other	Circulating Markers of Inflammation	Plasma CRP, IL-1ß, IL-6, and TNF-a will be measured using ELISA	Baseline
Other	Cytokine secretion from lipopolysaccharide(LPS)-stimulated peripheral blood mononuclear cells (PBMCs)	PBMCs will be isolated from heparinized whole blood using Cell Preparation Tube, PBMCs will be cultured with LPS, and supernatants will be harvested after 4-hour stimulation at 37°C. IL-1ß, IL-6, and TNF-a in the supernatants will be measured using ELISA.	Baseline
Other	Distribution of Monocyte Subsets	PBMCs will be stained with fluorescence-labeled antibodies for monocyte (CD14 and CD16) and analyzed using an LSR II flow cytometer.	Baseline
Other	Ex Vivo Nitric Oxide Production from Human Umbilical Vein Endothelial Cells (HUVECs)	HUVECs will be incubated with basal media supplemented with 10% human serum collected from participants and stained with the fluorescent probe DAF-FM diacetate to detect nitric oxide production production in response to acetylcholine.	Baseline
Other	Ex Vivo Reactive Oxygen Species Production from Human Umbilical Vein Endothelial Cells (HUVECs)	HUVECs will be incubated with basal media supplemented with 10% human serum collected from participants and stained with the fluorescent probe DAF-FM diacetate to detect reactive oxygen species production in response to acetylcholine.	Baseline
Primary	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
Secondary	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
Secondary	Serum Sex Hormones	Serum sex hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, prolactin, sex hormone binding globulin (SHBG), and anti-mullerian hormone (AMH)] will be measured using chemiluminescent assays.	Baseline
Secondary	Urinary Sex Hormones	Urinary sex hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrone-3-glucuronide (E1c), and pregnanediol-3-glucuronide (Pdg)] will be measured by by chemiluminescent assays using ACS-180 Autoanalyzer.	Baseline