Clinical trial NCT02042196: Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women
Official title: Biological Mechanisms of Vascular Dysfunction With Age and Estrogen Deficiency
Conditions: Menopause
Aging
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.
Interventions:
description: 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.
name: KUVAN
other_name: Tetrahydrobiopterin or BH4
type: Drug
description: Placebo pills designed to match the dissolvable KUVAN pills
name: Placebo
other_name: Control
type: Drug
description: Cetrotide (0.25mg/d) will be taken daily for 10 days via abdominal subcutaneous injection.
name: Cetrotide
other_name: Cetrorelix acetate
type: Drug
description: 0.075mg/d transdermal patch will be placed on skin.
name: Climara
other_name: Estradiol transdermal patch
type: Drug
description: Inactive transdermal patch
name: Placebo transdermal patch
other_name: Control
type: Drug
Study arms:
design_group_description: Baseline experiment: Subjects randomized to either 1) KUVAN (10mg/kg body weight) crossover to placebo OR 2) placebo crossover to KUVAN<br/>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
design_group_title: Pre or Early perimenopausal 1
design_group_type: Experimental
design_group_description: Baseline experiment: Subjects randomized to either 1) KUVAN crossover to placebo OR 2) placebo crossover to KUVAN<br/>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
design_group_title: Pre or Early Perimenopausal 2
design_group_type: Experimental
design_group_description: Subjects randomized to either 1) KUVAN crossover to placebo OR 2) placebo crossover to KUVAN<br/>No hormone modification.
design_group_title: Late Perimenopausal and Postmenopausal
design_group_type: Experimental
Sponsor: University of Colorado Denver
Collaborators: National Heart, Lung & Blood Institute
Drug name mappings:
name: 醋酸西曲瑞克
lang: CN
name: Cetrorelix
lang: EN
name: セトロレリクス酢酸塩
lang: JP
name: 盐酸沙丙蝶呤
lang: CN
name: Sapropterin Dihydrochloride
lang: EN
name: サプロプテリン塩酸塩
lang: JP
name: 雌二醇
lang: CN
name: Estradiol
lang: EN
name: エストラジオール
lang: JP