Effects of Ovarian Hormone Suppression on Vascular and Cognitive Function

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT03112226
• Collaborator: (none)
• Enrollment: 19
• Locations: 2
• Arms: 2
• Actual Duration (Months): 28.4
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Cognitive Impairment; Estrogen Deficiency; Menopause; Endothelial Dysfunction; Vascular Stiffness	Other: GnRHant + E2; Other: GnRHant + Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Effects of Ovarian Hormone Suppression on Vascular and Cognitive Function
• Actual Study Start Date: Feb 7, 2018
• Actual Primary Completion Date: Jun 6, 2020
• Actual Study Completion Date: Jun 21, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: GnRHant + E2 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; GnRH antagonist with estradiol add-back; Other Names: Degarelix acetate, Firmagon + Estradiol, Climara transdermal system
Placebo Comparator: GnRHant + Placebo Single dose of GnRH antagonist degarelix acetate for depot injection (80mg) Transdermal placebo patch, weekly for 12 weeks	Other: GnRHant + Placebo; GnRH antagonist with placebo add-back; Other Names: Degarelix acetate, Firmagon

Outcome Measures

Primary Outcome Measures

1. Changes in Prefrontal cortex brain activation [Baseline, 3 months]

   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

1. Changes in Endothelial function [Baseline, 3 months]

   Endothelial function will be measured using brachial artery flow-mediated dilation at baseline and 3 months

2. Changes in Arterial stiffness [Baseline, 3 months]

   Carotid artery compliance will be measured using ultrasound at baseline and 3 months

3. Changes in Executive cognitive function [Baseline, 3 months]

   Changes in executive cognitive function on a battery of neuropsychological tests will be measured at baseline and 3 months

Other Outcome Measures

1. Changes in Mitochondrial dysfunction [Baseline and 3 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Anschutz Medical Campus	Aurora	Colorado	United States	80045
2	University of Colorado Boulder Intermountain Neuroimaging Consortium	Boulder	Colorado	United States	80309

Sponsors and Collaborators

• University of Colorado, Denver

Investigators

• Principal Investigator: Kerry L Hildreth, MD, University of Colorado, Denver

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT03112226
• Other Study ID Numbers: 17-0092
• First Posted: Apr 13, 2017
• Last Update Posted: Jun 7, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Colorado, Denver: cognitive impairment; menopause; estrogen; functional MRI; executive function; endothelial function; arterial stiffness
• Additional relevant MeSH terms: Cognitive Dysfunction; Estradiol; LHRH, N-acetyl-(4-chlorophenylalanyl)(1)-(4-chlorophenylalanyl)(2)-tryptophyl(3)-arginyl(6)-alanine(10)-

Study Results

No Results Posted as of Jun 7, 2021