Estrogen Deficiency on Cardiovascular Risk

Cardiovascular Diseases Clinical Trial

Official title:

Estrogen Deficiency on Cardiovascular Risk: Sympathetic Responses and Pro-inflammatory Cytokines

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06369363
• Other study ID #: STUDY000024245
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: September 2025
• Est. completion date: November 2027

Study information

• Verified date: April 2024
• Source: Milton S. Hershey Medical Center
• Contact: Lu Qin, PhD
• Phone: 4026096068
• Email: lqin[@]pennstatehealth.psu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To explore how estrogen deficiency impacts the blood pressure (BP) and sympathetic nerve activity (SNA), and how it impacts the production of the key pro-inflammatory mediators such as Tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). It is hypothesized that estrogen deficiency increases BP, SNA and the pathway activities of the key pro-inflammatory mediators. Those effects are impacted through the downregulation of the estrogen receptor.

Description:

In the United States, cardiovascular disease (CVD) is one of the major health concerns and affects approximately 6.5 million people over 40. As the number of elderly women increases, CVD becomes an increasing problem. Estrogen is cardioprotective, and the menopause condition in the aging female population induces the loss of this protective effect. There has been a dilemma for medical treatment in CVD patients with comorbidities including endometriosis or breast cancer history. Overall, these patients lose the cardioprotective effect of estrogen and increase the risk of CVD development. However, there is still little understanding regarding the mechanism for how estrogen suppression in women accelerates CVD development. The proposed studies are, therefore, the essential first step to elucidating how estrogen alters mechanisms underlying CVD and provide the preclinical data to design studies for future alternative intervention strategies for CVD patients undergoing estrogen suppression therapies.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: November 2027
• Est. primary completion date: September 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 54 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age 54-75 years

• Healthy participants who are capable of giving informed consent

• Classified as postmenopausal or stop having period >1year or had a full hysterectomy surgery

• Any race or ethnicity

• Have satisfactory history and physical exam

• Free of acute medical conditions

Exclusion Criteria:

• <54 or >75 years

• Medications that could alter cardiovascular, thermoregulatory, or peripheral vascular control (e.g. Angiotensin converting enzyme inhibitors, statins, beta blockers, etc.);

• Self-reported history of long-term menstrual irregularities, vaginal bleeding, or other gynecological conditions that could influence study outcomes

• Use of hormone therapy during 6 months prior to study enrollment

• Allergy to latex

• Current smoker

• Have any clinically relevant history or the presence of metabolic (e.g., diabetes), respiratory, renal, hepatic, gastrointestinal, hematological, lymphatic, neurological, cardiovascular, or other disease or diseases that, in the opinion of the research team, exclude the subject from participation.

• Presenting with a resting blood pressure of 150/100 or higher

• Contraindications to a maximal exercise test or an indication for early termination of an exercise test

• Taking any medications that affect vascular control or autonomic function (e.g. beta blockers, ACE inhibitors, calcium channel blockers, etc.)

• Contraindications to estrogen patch: include undiagnosed vaginal bleeding; known, suspected, or history of breast cancer; known or suspected E2-sensitive neoplasm; history of deep venous thrombosis or pulmonary embolism; current or recent arterial thromboembolic disease; liver dysfunction and disease; known or suspected pregnancy.

• Past/current history of venous thromboembolism, hypercoagulation or thrombopenia

• Past/current history of hormone-responsive cancer

• Past/current history of endometrial hyperplasia

• Patient has a recent drug or alcohol abuse history (less than 6 months) or is currently using or abusing excessive alcohol or drugs. Excessive alcohol will be defined as greater than 14 drinks per week.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Postmenopausal Symptoms

Intervention

Drug:
• Placebo
Subjects will be assigned to 1 week of transdermal placebo patch.
• Estradiol
Subjects will be assigned to 1 week of transdermal estradiol (0.05 mg/day) patch.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Red blood cell flux	Percentage relative to the maximum flux level	Recorded continuously for up to 4 hours during the study visit
Primary	Mean arterial pressure (mmHg)	Calculated from the systolic and diastolic blood pressure	Recorded continuously for up to 4 hours during the study visit
Primary	baseline plasma TNF-a concentration (pg/ml)	Measured by ELISA kits	Upon participants' arrival to the first study visit up to 5 minutes
Primary	One week post-intervention plasma TNF-a concentration (pg/ml)	Measured by ELISA kits	Upon participants' arrival to the second study visit (1 week after the first visit)
Primary	baseline plasma IL-1ß concentration (pg/ml)	Measured by ELISA kits	Upon participants' arrival to the first study visits up to 5 minutes
Primary	One week post-intervention plasma IL-1ß concentration (pg/ml)	Measured by ELISA kits	Upon participants' arrival to the second study visit (1 week after the first visit)
Primary	baseline plasma IL-6 concentration (pg/ml)	Measured by ELISA kits	Upon participants' arrival to the first study visits up to 5 minutes
Primary	One week post-intervention plasma IL-6 concentration (pg/ml)	Measured by ELISA kits	Upon participants' arrival to the second study visit (1 week after the first visit)
Secondary	baseline plasma estrogen (pg/ml)	Measured by ELISA kits	Upon participants' arrival to the first study visits up to 5 minutes
Secondary	One week post-intervention plasma estrogen (pg/ml)	Measured by ELISA kits	Upon participants' arrival to the second study visit (1 week after the first visit)