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Effects of Ovarian Hormone Suppression on Vascular and Cognitive Function

Primary Purpose

Cognitive Impairment, Estrogen Deficiency, Menopause

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
GnRHant + E2
GnRHant + Placebo
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Cognitive Impairment focused on measuring cognitive impairment, menopause, estrogen, functional MRI, executive function, endothelial function, arterial stiffness

Eligibility Criteria

18 Years - 50 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

Sites / Locations

  • University of Colorado Anschutz Medical Campus
  • University of Colorado Boulder Intermountain Neuroimaging Consortium

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

GnRHant + E2

GnRHant + Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Changes in Endothelial function
Endothelial function will be measured using brachial artery flow-mediated dilation at baseline and 3 months
Changes in Arterial stiffness
Carotid artery compliance will be measured using ultrasound at baseline and 3 months
Changes in Executive cognitive function
Changes in executive cognitive function on a battery of neuropsychological tests will be measured at baseline and 3 months

Full Information

First Posted
April 7, 2017
Last Updated
June 3, 2021
Sponsor
University of Colorado, Denver
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1. Study Identification

Unique Protocol Identification Number
NCT03112226
Brief Title
Effects of Ovarian Hormone Suppression on Vascular and Cognitive Function
Official Title
Effects of Ovarian Hormone Suppression on Vascular and Cognitive Function
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
February 7, 2018 (Actual)
Primary Completion Date
June 6, 2020 (Actual)
Study Completion Date
June 21, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cognitive Impairment, Estrogen Deficiency, Menopause, Endothelial Dysfunction, Vascular Stiffness
Keywords
cognitive impairment, menopause, estrogen, functional MRI, executive function, endothelial function, arterial stiffness

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GnRHant + E2
Arm Type
Active Comparator
Arm Description
Single dose of GnRH antagonist degarelix acetate for depot injection (80mg) Transdermal estradiol add-back; Climara patch, 0.075mg/day, weekly for 12 weeks
Arm Title
GnRHant + Placebo
Arm Type
Placebo Comparator
Arm Description
Single dose of GnRH antagonist degarelix acetate for depot injection (80mg) Transdermal placebo patch, weekly for 12 weeks
Intervention Type
Other
Intervention Name(s)
GnRHant + E2
Other Intervention Name(s)
Degarelix acetate, Firmagon + Estradiol, Climara transdermal system
Intervention Description
GnRH antagonist with estradiol add-back
Intervention Type
Other
Intervention Name(s)
GnRHant + Placebo
Other Intervention Name(s)
Degarelix acetate, Firmagon
Intervention Description
GnRH antagonist with placebo add-back
Primary Outcome Measure Information:
Title
Changes in Prefrontal cortex brain activation
Description
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
Time Frame
Baseline, 3 months
Secondary Outcome Measure Information:
Title
Changes in Endothelial function
Description
Endothelial function will be measured using brachial artery flow-mediated dilation at baseline and 3 months
Time Frame
Baseline, 3 months
Title
Changes in Arterial stiffness
Description
Carotid artery compliance will be measured using ultrasound at baseline and 3 months
Time Frame
Baseline, 3 months
Title
Changes in Executive cognitive function
Description
Changes in executive cognitive function on a battery of neuropsychological tests will be measured at baseline and 3 months
Time Frame
Baseline, 3 months
Other Pre-specified Outcome Measures:
Title
Changes in Mitochondrial dysfunction
Description
Measures of mitochondrial function including dynamics (fusion, fission), antioxidant defense and biogenesis will be measured in mitochondria isolated from peripheral blood mononuclear cells at baseline and 3 months.
Time Frame
Baseline and 3 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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) Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kerry L Hildreth, MD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado Anschutz Medical Campus
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Colorado Boulder Intermountain Neuroimaging Consortium
City
Boulder
State/Province
Colorado
ZIP/Postal Code
80309
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Effects of Ovarian Hormone Suppression on Vascular and Cognitive Function

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