Trial record 10 of 205 for:    heart disease AND women OR coronary microvascular disease OR cardiac syndrome X | Open Studies | NIH, U.S. Fed

Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women (SHAPE2)

This study is currently recruiting participants.
Verified January 2014 by University of Colorado, Denver
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Kerrie Moreau, University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT02042196
First received: January 17, 2014
Last updated: NA
Last verified: January 2014
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Menopause
Aging
Vascular Health
Drug: KUVAN
Drug: Placebo
Drug: Cetrotide
Drug: Climara
Drug: Placebo transdermal patch
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Biological Mechanisms of Vascular Dysfunction With Age and Estrogen Deficiency

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Change in brachial artery flow-mediated dilation [ Time Frame: 4-5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in carotid artery compliance and endothelial cell protein expression [ Time Frame: 4-5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: December 2013
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pre or Early perimenopausal 1

Baseline 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

Drug: KUVAN
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.
Other Name: Tetrahydrobiopterin or BH4
Drug: Placebo
Placebo pills designed to match the dissolvable KUVAN pills
Drug: Cetrotide
Cetrotide (0.25mg/d) will be taken daily for 10 days via abdominal subcutaneous injection.
Other Name: Cetrorelix acetate
Drug: Placebo transdermal patch
Experimental: Pre or Early Perimenopausal 2

Baseline 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

Drug: KUVAN
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.
Other Name: Tetrahydrobiopterin or BH4
Drug: Placebo
Placebo pills designed to match the dissolvable KUVAN pills
Drug: Cetrotide
Cetrotide (0.25mg/d) will be taken daily for 10 days via abdominal subcutaneous injection.
Other Name: Cetrorelix acetate
Drug: Climara
0.075mg/d transdermal patch will be placed on skin.
Other Name: Estradiol transdermal patch
Experimental: Late Perimenopausal and Postmenopausal

Subjects randomized to either 1) KUVAN crossover to placebo OR 2) placebo crossover to KUVAN

No hormone modification.

Drug: KUVAN
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.
Other Name: Tetrahydrobiopterin or BH4
Drug: Placebo
Placebo pills designed to match the dissolvable KUVAN pills

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT02042196

Contacts
Contact: Amber Palumbo 720-848-6475 Amber.Palumbo@ucdenver.edu

Locations
United States, Colorado
University of Colorado Denver Recruiting
Aurora, Colorado, United States, 80045
Contact: Kerrie Moreau, PhD    303-724-1914    kerrie.moreau@ucdenver.edu   
Principal Investigator: Kerrie Moreau, PhD         
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Kerrie Moreau, PhD University of Colorado School of Medicine
  More Information

No publications provided

Responsible Party: Kerrie Moreau, Associate Professor of Medicine, University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02042196     History of Changes
Other Study ID Numbers: 06-0537 SHAPE2
Study First Received: January 17, 2014
Last Updated: January 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
endothelial function
women
estrogen deficiency
sex hormones
adiposity
oxidative stress
antioxidants

Additional relevant MeSH terms:
Estradiol
Estrogens
Hormones
Cetrorelix
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Hormone Antagonists

ClinicalTrials.gov processed this record on April 17, 2014