Ovarian Hormone Regulation of Central and Cerebrovascular Hemodynamics (NoMEN Study)

Ovarian Hormone Regulation of Central and Cerebrovascular Hemodynamics

This study will evaluate changes in blood vessels around the heart (e.g., aorta and carotid arteries) and in the brain with the loss of female sex hormones (e.g., estrogen) during the menopause transition. The menopause transition is associated with declines in blood vessel function and increased risk for cardiovascular disease and Alzheimer's disease. Increasing evidence supports an early role for declines in blood vessel function and future development of Alzheimer's disease in aging men and women. This study will learn about the effects of changes in female sex hormones, such as estrogen, during the menopause transition on blood vessel around the heart and in the brain in women.

Study Overview

• Status: Active, not recruiting
• Conditions: Menopause; Aging; Estrogen Deficiency; Women
• Intervention / Treatment: Drug: GnRH antagonist

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lyndsey DuBose, PhD; Phone Number: 720-848-5596; Email: lyndsey.dubose@cuanschutz.edu
• Study Contact Backup: Name: Kerrie Moreau, PhD; Phone Number: (303)724-1914; Email: kerrie.moreau@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria: Healthy premenopausal, early perimenopausal and postmenopausal women will be recruited. Premenopausal women will have regular menstrual cycles, with no change in observed cycle length (21-35 days), confirmed by menstrual cycle calendars. Early perimenopausal will be defined as a change in cycle length of >7 days from normal with no skipped periods and/or a FSH <25 IU/L (with discretion of the study MD). Postmenopausal women will have gone through natural (i.e., non-surgical) menopause with >12 months but <6 years of amenorrhea. We will make a major effort to ensure that the women enrolled in this study come from all races and ethnicities and a wide range of socioeconomic and educational levels.

Exclusion Criteria:

• Seated resting blood pressure >140/90 mmHg
• Use of medications that might influence cardiovascular function or cerebral blood flow;
• Pregnant, currently breastfeeding or intention to become pregnant in the next 6 months;
• Use of menopausal therapy or hormonal contraceptives, etc. within the previous 3 months or intent to start during the study period;
• BMI >39 kg/m2;
• Vigorous intensity exercise >2 days per week;
• Any current or past history of systemic illness that would interfere with study outcomes such as: diabetes, cancer (other than melanoma), liver, gallbladder disease, peripheral artery disease or thromboembolism, neurological disease, CVD or cerebrovascular disease;
• Abnormal thyroid, liver, or kidney function testing during the screening examination or bloodwork;
• Plasma glucose >126 mg/dl under fasting conditions;
• Smoking or living with a smoker within the past 12 months;
• Current or planned participation in an interventional study during the present study or unwillingness to complete study-related procedures;
• Patients who report active acute systemic infection (e.g., flu, common cold, etc), fever (> 100.0 °F) or feeling ill will be asked to delay vascular testing until they are no longer febrile or ill. Additionally, anyone who has experienced a serious illness (requiring hospitalization) within the last 6 months, had a confirmed positive COVID test and hospitalized, or anyone with a confirmed positive COVID test within the last 6 months will be ineligible to participate (discretion of the study PI and MD).
• No use of vitamin/supplements or chronic use of anti-inflammatory medications, or willingness to stop 1 month prior to the vascular visit.

In premenopausal women participating in the intervention:

• Contraindications to Degarelix including hypersensitivity to degarelix acetate, extrinsic peptide hormones, mannitol, GnRH, benzyl alcohol (the vehicle for injection of degarelix acetate)
• Undiagnosed vaginal bleeding
• Osteopenia or osteoporosis (i.e., proximal femur or lumbar spine DXA Z scores <-1.0)
• CES-D score ≥16 (unless clinician follow-up and clinical judgement determine they are eligible (will be noted in study chart)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Premenopausal Group: GnRH antagonist; Gonadotropin releasing hormone (GnRH) antagonist is degarelix acetate, 80 mg, delivered once as a subcutaneous injection.	Drug: GnRH antagonist; GnRH antagonist will be given once for premenopausal women (12-week intervention) and twice for postmenopausal women (24-week intervention); Other Names: Degarelix acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aortic stiffness and pulsatile hemodynamics	Aortic characteristic impedance and forward pressure wave amplitude	Change from baseline at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Common carotid artery stiffness and pulsatile hemodynamics	Carotid characteristic impedance and forward pressure wave amplitude	Change from baseline at 12 weeks
Macrovascular cerebral blood flow	Cerebral blood flow measured by transcranial Doppler	Change from baseline at 12 weeks
Macrovascular cerebrovascular reserve	Breath hold index measured by transcranial Doppler	Change from baseline at 12 weeks
Microvascular cerebral blood flow	Cerebral blood flow measured by Arterial Spin Labeling Magnetic Resonance Imaging	Change from baseline at 12 weeks

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Lyndsey DuBose, PhD, University of Colorado Denver Anschutz Medical Campus

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2021
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: September 16, 2021
• First Submitted That Met QC Criteria: September 16, 2021
• First Posted (Actual): September 27, 2021

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 21-3590

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: No