Effects of Ovarian Hormone Suppression on Vascular and Cognitive Function

NCT03112226 | Completed

• 1 other identifier: 17-0092
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

Complaints about memory and thinking are common in women as they go through menopause. The female hormone estrogen is important for both the health of both the brain and the blood vessels. In Alzheimer's disease there is damage to the blood vessels in the brain. This study will look at how the loss of the female hormone estrogen affects brain function and the health of blood vessels.

Conditions

Cognitive Impairment; Estrogen Deficiency; Menopause; Endothelial Dysfunction; Vascular Stiffness

Keywords

cognitive impairment; menopause; estrogen; functional MRI; executive function; endothelial function; arterial stiffness

Outcome Measures

Primary Outcomes (1)

• Changes in Prefrontal cortex brain activation

  Changes in patterns of brain activation in the prefrontal cortex using functional magnetic resonance imaging (fMRI) during a task of working memory will be measured at baseline and 3 months

  Baseline, 3 months

Secondary Outcomes (3)

• Changes in Endothelial function

  Baseline, 3 months

• Changes in Arterial stiffness

  Baseline, 3 months

• Changes in Executive cognitive function

  Baseline, 3 months

Other Outcomes (1)

• Changes in Mitochondrial dysfunction

  Baseline and 3 months

Study Arms (2)

GnRHant + E2

ACTIVE COMPARATOR

Single dose of GnRH antagonist degarelix acetate for depot injection (80mg) Transdermal estradiol add-back; Climara patch, 0.075mg/day, weekly for 12 weeks

Other: GnRHant + E2

GnRHant + Placebo

PLACEBO COMPARATOR

Single dose of GnRH antagonist degarelix acetate for depot injection (80mg) Transdermal placebo patch, weekly for 12 weeks

Other: GnRHant + Placebo

Interventions

GnRHant + E2 OTHER

GnRH antagonist with estradiol add-back

Also known as: Degarelix acetate, Firmagon + Estradiol, Climara transdermal system

GnRHant + E2

GnRHant + Placebo OTHER

GnRH antagonist with placebo add-back

Also known as: Degarelix acetate, Firmagon

GnRHant + Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Stages of Reproductive Aging Workshop (STRAW+10) peak or late reproductive stage (-4, -3b or -3a)
• Healthy based on medical history, physical examination and standard blood chemistries
• Normotensive (resting blood pressure \<140/90 mmHg)
• Normoglycemia (fasting glucose \<110mg/dl and hemoglobin A1c\<6.5%)
• Non-smoker (for at least 12 months)

You may not qualify if:

• Serum Follical Stimulating Hormone (FSH) \>25mIU/mL measured during the first 5 days of the menstrual cycle
• Use of hormonal therapy within the past 3 months
• Use of antihypertensive or lipid-lowering medications
• Pregnant or lactating, or planning to become pregnant during the study period
• Known hypersensitivity to any of the study medications
• Abnormal vaginal bleeding
• History of venous thromboembolism or hormone-sensitive cancer
• History of neurologic disease or major psychiatric illness
• History of diagnosed learning disability or less than high-school education
• Contraindication to Magnetic Resonance Imaging (MRI) scanning
• Depression (Center for Epidemiological Studies - Depression (CESD) score \>16)
• Significant cognitive impairment (Mini Mental State Examination (MMSE) score \<27)
• Severe osteopenia or osteoporosis (proximal femur or lumbar spine T-score \< -2.0)
• Body Mass Index (BMI) \>40kg/m2

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (2)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

University of Colorado Boulder Intermountain Neuroimaging Consortium

Boulder, Colorado, 80309, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

LHRH, N-acetyl-(4-chlorophenylalanyl)(1)-(4-chlorophenylalanyl)(2)-tryptophyl(3)-arginyl(6)-alanine(10)-; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; Estradiol

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Kerry L Hildreth, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2017
• First Posted: April 13, 2017
• Study Start: February 7, 2018
• Primary Completion: June 6, 2020
• Study Completion: June 21, 2020
• Last Updated: June 7, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)