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Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women (SHAPE)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00608062
First received: January 31, 2008
Last updated: June 26, 2013
Last verified: June 2013

January 31, 2008
June 26, 2013
March 2007
June 2013   (final data collection date for primary outcome measure)
Arterial stiffness (carotid artery compliance) during saline and ascorbic acid [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00608062 on ClinicalTrials.gov Archive Site
  • Endothelial function - brachial artery flow-mediated dilation [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]
  • Endothelial cell protein expression [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]
  • Serum or plasma blood samples - endothelin-1, catecholamines, angiotensin converting enzyme, oxidative stress markers, Interleukin 6 (IL6), C-Reactive Protein (CRP), sex hormones, ascorbic acid, glucose, insulin [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]
  • Carotid and brachial blood pressures [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]
  • Endothelial function - brachial artery flow-mediated dilation [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]
  • Endothelial cell protein expression [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]
  • Serum or plasma blood samples - endothelin-1, catecholamines, angiotensin converting enzyme, oxidative stress markers, IL6, CRP, sex hormones, ascorbic acid, glucose, insulin [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]
  • Carotid and brachial blood pressures [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women
Biological Mechanisms of Arterial Stiffening With Age and Estrogen Deficiency

The purpose of this study is to find out why women's arteries stiffen as they go through menopause, and how this is affected by estrogen loss. We believe that arteries stiffen with the loss of estrogen because of "oxidative stress," the production of molecules that can damage cells and tissues in the body, and because the arteries lose their ability to expand, or dilate.

As women get older and go through menopause, estradiol levels decrease. Also with aging, the arteries that are located around the heart get stiffer. Over time this increase in arterial stiffness can lead to a number of health problems such as high blood pressure and heart disease. In this study we want to find out if a short-term drop in estrogen levels in premenopausal and perimenopausal women can cause arteries to become stiffer, and why this happens. Additionally, in postmenopausal women, we want to find out if a short-term increase in estrogen levels causes their arteries to become more flexible (less stiff).

Arterial health (i.e., stiffness) will be examined in premenopausal, perimenopausal and postmenopausal women before and after they are given a drug called Ganirelix™ (for 7 days), which will markedly lower their reproductive hormones. After the first 4 days of taking Ganirelix™, the women will be randomly placed into 1 of 2 treatment groups to take either estrogen (0.075 mg/d skin patch) replacement or placebo for the rest of the Ganirelix treatment. This is to increase estrogen levels back to the normal level. After having the patch on for 4 days, arterial health will be examined again.

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
  • Arterial Stiffening
  • Aging
  • Menopause
  • Drug: GnRHant - Ganirelix acetate
    1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7
    Other Name: Ganirelix
  • Drug: Transdermal estradiol patch
    0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
  • Drug: Transdermal placebo patch
    Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
  • Experimental: Pre1
    Premenopausal - GnRHant plus estradiol
    Interventions:
    • Drug: GnRHant - Ganirelix acetate
    • Drug: Transdermal estradiol patch
  • Placebo Comparator: Pre2
    Premenopausal - GnRHant plus placebo
    Interventions:
    • Drug: GnRHant - Ganirelix acetate
    • Drug: Transdermal placebo patch
  • Experimental: Peri1
    Perimenopausal (early) - GnRHant plus estradiol
    Interventions:
    • Drug: GnRHant - Ganirelix acetate
    • Drug: Transdermal estradiol patch
  • Placebo Comparator: Peri2
    Perimenopausal (early) - GnRHant plus placebo
    Interventions:
    • Drug: GnRHant - Ganirelix acetate
    • Drug: Transdermal placebo patch
  • Experimental: Peri3
    Perimenopausal (late) - GnRHant plus estradiol
    Interventions:
    • Drug: GnRHant - Ganirelix acetate
    • Drug: Transdermal estradiol patch
  • Placebo Comparator: Peri4
    Perimenopausal (late) - GnRHant plus placebo
    Interventions:
    • Drug: GnRHant - Ganirelix acetate
    • Drug: Transdermal placebo patch
  • Experimental: Post1
    Postmenopausal - GnRHant plus estradiol
    Interventions:
    • Drug: GnRHant - Ganirelix acetate
    • Drug: Transdermal estradiol patch
  • Placebo Comparator: Post2
    Postmenopausal - GnRHant plus placebo
    Interventions:
    • Drug: GnRHant - Ganirelix acetate
    • Drug: Transdermal placebo patch

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
92
June 2013
June 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Healthy women of all races and ethnic backgrounds in one of the following groups:

    • Premenopausal: 18-49 years, regular menstrual cycles with no change in observed cycle length (21-35 days)
    • Perimenopausal: 40-55 years, categorized as either early (at least 2 cycles with cycle length changes of at least 7 days) or late (more than 3 months of amenorrhea) transition
    • Postmenopausal: 45-70 years, more than 12 months of amenorrhea as defined by the menopausal staging system (STRAW); additionally, postmenopausal women will be categorized into early and late stages as defined by the STRAW definition, specifically, women who are less than 5 years postmenopause will be considered early, and women more than 6 years will be categorized as late
  • All postmenopausal women will have undergone natural menopause
  • No oral contraceptive or Hormone Replacement Therapy (HRT) use for at least 6 months
  • Resting blood pressure less than 140/90 mmHg
  • Plasma glucose concentrations less than 110 mg/dl under fasting conditions
  • Sedentary or recreationally active (less than 3 days of vigorous aerobic exercise)
  • No use of medications that might influence cardiovascular function
  • Nonsmokers
  • No use of vitamin supplements or willing to stop use for duration of the study

Exclusion Criteria:

  • History of or active estrogen-dependent neoplasms, acute liver or gallbladder disease, vaginal bleeding, venous thromboembolism, hypertriglyceridemia, and cardiovascular disease
  • Known allergy to transdermal patch or GnRHant
  • Other contraindications to HRT and GnRHant
Female
18 Years to 70 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00608062
06-0537, R01AG027678
No
University of Colorado, Denver
University of Colorado, Denver
National Institute on Aging (NIA)
Principal Investigator: Kerrie L Moreau, PhD University of Colorado, Denver
University of Colorado, Denver
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP