Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women
SHAPE2
Biological Mechanisms of Vascular Dysfunction With Age and Estrogen Deficiency
2 other identifiers
interventional
100
1 country
1
Brief Summary
As women get older and go through menopause, levels of the female reproductive hormone estradiol decrease to low levels. Also with aging, the functioning of the arteries declines. Over time this vascular dysfunction can lead to health problems such as high blood pressure and heart disease. This study is being done to help determine what causes arteries to become unhealthy in postmenopausal women, who have low levels of the female reproductive hormone estradiol. In this study we will test whether low levels of tetrahydrobiopterin (BH4), a natural substance in the body that can cause the arteries to expand, explains why arteries become unhealthy in women with low levels of estradiol. To answer this question, we will study how vascular function changes with a medication that causes a short-term increase in BH4 levels when estradiol is lowered with a medication, compared to when estradiol is normal. We will also determine whether the administration of the antioxidant vitamin C, along with the medication to increase BH4 levels, will normalize vascular health in perimenopausal and postmenopausal women, and in women who have their estradiol levels lowered.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for early_phase_1
Started Dec 2013
Typical duration for early_phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2013
CompletedFirst Submitted
Initial submission to the registry
January 17, 2014
CompletedFirst Posted
Study publicly available on registry
January 22, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 2, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
May 2, 2016
CompletedJuly 11, 2019
July 1, 2019
2.4 years
January 17, 2014
July 9, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in brachial artery flow-mediated dilation
4-5 years
Secondary Outcomes (1)
Change in carotid artery compliance and endothelial cell protein expression
4-5 years
Study Arms (3)
Pre or Early perimenopausal 1
EXPERIMENTALBaseline experiment: Subjects randomized to either 1) KUVAN (10mg/kg body weight) crossover to placebo OR 2) placebo crossover to KUVAN Hormone modification: GnRH antagonist with Cetrotide (0.25mg/d) + placebo transdermal patch, then subjects randomized again to either 1) KUVAN crossover to placebo OR 2) placebo crossover to KUVAN
Pre or Early Perimenopausal 2
EXPERIMENTALBaseline experiment: Subjects randomized to either 1) KUVAN crossover to placebo OR 2) placebo crossover to KUVAN Hormone modification: Estrogen add-back with Cetrotide + Climara (0.075mg/d), then subjects randomized again to either 1) KUVAN crossover to placebo OR 2) placebo crossover to KUVAN
Late Perimenopausal and Postmenopausal
EXPERIMENTALSubjects randomized to either 1) KUVAN crossover to placebo OR 2) placebo crossover to KUVAN No hormone modification.
Interventions
KUVAN will be given orally at 10mg/kg dose per body weight. KUVAN will be dissolved in 4-8oz water and consumed within 15 minutes.
Placebo pills designed to match the dissolvable KUVAN pills
Cetrotide (0.25mg/d) will be taken daily for 10 days via abdominal subcutaneous injection.
0.075mg/d transdermal patch will be placed on skin.
Inactive transdermal patch
Eligibility Criteria
You may qualify if:
- age criteria established for pre-, peri- and postmenopausal women, and if postmenopausal at least 1 year beyond menopause
- resting blood pressure \<140/90 mmHg 81; 2) plasma glucose concentrations \<110 mg/dl under fasting conditions
- sedentary or recreationally active (\<3 days of vigorous aerobic exercise)
- no use of OCs, HT, or other medications that might influence cardiovascular function
- nonsmokers
- no use of vitamin supplements, NSAIDS or willing to stop use for duration of the study
- not taking any other medications that would interact with cetrotide, E2 patch, or Kuvan® to confound interpretation of results
You may not qualify if:
- history of or active estrogen-dependent neoplasms, acute liver or gallbladder disease, vaginal bleeding, venous thromboembolism, hypertriglyceridemia, and CVD
- known allergy to transdermal patch, GnRHant (i.e., hypersensitivity to cetrorelix, extrinsic peptide hormones, mannitol, GnRH, benzyl alcohol - the vehicle for injection of cetrorelix), or KUVAN
- history of stomach ulcer or bleeding
- other contraindications to HRT, GnRHant, and KUVAN (i.e., taking Levodopa, medications that can inhibit folate metabolism including methotrexate)
- pregnant or currently breastfeeding
- Other conditions for which individuals will be excluded from the study include: diabetes, active infection, history of seizures or disease that affects the nervous system, sepsis or an abnormal resting ECG
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Colorado Denver
Aurora, Colorado, 80045, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Kerrie Moreau, PhD
University of Colorado School of Medicine
Study Design
- Study Type
- interventional
- Phase
- early phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 17, 2014
First Posted
January 22, 2014
Study Start
December 1, 2013
Primary Completion
May 2, 2016
Study Completion
May 2, 2016
Last Updated
July 11, 2019
Record last verified: 2019-07