Perimenopausal Estrogen Replacement Therapy Study (PERT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of North Carolina, Chapel Hill
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Susan Girdler, PhD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01308814
First received: February 28, 2011
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

Study Background and Objectives: In the U.S. the majority of heart disease deaths are in women, not men. Much of the gender disparity in CVD rates relate to the burden of CV risk in women after the menopause. Depression has been associated with an increased risk for CVD morbidity and mortality. Even histories of recurrent depression in euthymic individuals are associated with elevated CV risk. Understanding the depression-CVD link may have particular relevance for women since women experience depression at a rate twice that of men. Substantial convergent evidence indicates that ovarian failure (estrogen deprivation) is one likely mechanism contributing to both CVD and depression in women. The perimenopause, a time associated with a two-fold increase in rates of depression, may provide an ideal opportunity for studying the pathophysiology of CV risk and depression in women.

The primary objective of this study is to examine the prophylactic role of estradiol in the development of depressive symptoms and the progression of cardiovascular risk in perimenopausal women with or without histories of depression. The investigators predict that women susceptible to depression will be particularly vulnerable to the acceleration of CVD in the context of the perimenopause and, consequently, will show differentially greater benefit of estradiol treatment during the menopause transition for both indices of CV risk (e.g. inflammation, endothelial function, stress reactivity), as well as depressive symptoms.


Condition Intervention Phase
Perimenopause
Menopause
Depression
Drug: Estradiol
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Depression, Estrogen Replacement, and Cardiovascular Health in the Perimenopause

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Change in Depressive Symptoms as Indicated by The Center for Epidemiologic Studies Depression Scale (CES-D) [ Time Frame: Baseline, month 1, 2, 4, 6, 8, 10, 12 ] [ Designated as safety issue: No ]
  • Change in Psychiatric Diagnosis as Assessed by the Structured Clinical Interview for DSM Disorders I/NP [ Time Frame: Baseline and when prompted by CES-D score ] [ Designated as safety issue: No ]
  • Change in Stress Reactivity during Laboratory Session including Trier Social Stress Test [ Time Frame: Baseline, month 6 and 12 ] [ Designated as safety issue: No ]
    Primary measures reflecting stress reactivity will consist of mean arterial pressure (MAP), vascular resistance index (VRI), plasma cortisol, and plasma IL-6. For each of these four measures, a delta score (change from rest to stress) will be calculated and then standardized as Z scores. The individual Z scores will then be averaged to yield a single Stress Reactivity profile measure - a composite score reflecting magnitude of activation in the four primary stress-responsive pathways.


Secondary Outcome Measures:
  • Change in Functional Well-being as Assessed by the Medical Outcomes Study 36-item Short form (SF-36) [ Time Frame: Baseline, month 6 and 12 ] [ Designated as safety issue: No ]
  • Change in Metabolic risk [ Time Frame: Baseline, month 6 and 12 ] [ Designated as safety issue: No ]
    Subjects will be classified as having metabolic risk if they either meet standard criteria for the metabolic syndrome (based on 3 of 5 risk factors: elevated blood pressure, fasting triglycerides, fasting glucose, waist circumference and low HDL-cholesterol) or they exhibit insulin resistance based on the derivation of an insulin sensitivity index (ISI0,120 < 61) following the standard oral glucose tolerance test

  • Change in Flow Mediated Vasodilatation [ Time Frame: Baseline, month 6 and 12 ] [ Designated as safety issue: No ]
    Flow mediated vasodilatation of the brachial artery in response to reactive hyperemia using high resolution ultrasound, yielding a measure of endothelial-dependent vasodilatation.

  • Change in Baroreceptor sensitivity [ Time Frame: Baseline, month 6 and 12 ] [ Designated as safety issue: No ]
    Cardiac autonomic control via EKG measurement of HR and beat-to-beat changes in BP to assess baroreceptor sensitivity


Estimated Enrollment: 382
Study Start Date: October 2010
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo patches for 12 months and placebo pills for 12 days every 2 months.
Drug: Placebo
Placebo patches for 12 months, to be worn continuously and replaced once a week. Also, placebo pills will be administered for 12 days every 2 months.
Experimental: Estradiol
Transdermal 17β-estradiol (100 ug/day) for 12 months and oral micronized progesterone (200 mg/day) for 12 days every two months.
Drug: Estradiol
Transdermal 17β-estradiol (100 ug/day) for 12 months, administered as patches to be worn continuously and replaced once a week. Also, every 2 months, oral micronized progesterone (200 mg/day x 12 days) will be administered.
Other Name: Climara and Prometrium.

  Eligibility

Ages Eligible for Study:   45 Years to 60 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • must be between 45 and 60 years of age
  • must be in the menopause transition (irregular/ absent menstrual cycles or hot flashes)
  • must be are medically healthy

Exclusion Criteria:

- currently taking antidepressant medication

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01308814

Contacts
Contact: Leah Schrubbe, BA 919-972-7485 leah_schrubbe@med.unc.edu

Locations
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Leah Schrubbe, BA    919-972-7485    leah_schrubbe@med.unc.edu   
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Susan Girdler, PH.D. UNC
  More Information

No publications provided

Responsible Party: Susan Girdler, PhD, Principal Investigator, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01308814     History of Changes
Other Study ID Numbers: 10-0542, R01MH087619
Study First Received: February 28, 2011
Last Updated: February 5, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by University of North Carolina, Chapel Hill:
Perimenopause
Menopause
Depression
Cardiovascular health

Additional relevant MeSH terms:
Depressive Disorder
Mood Disorders
Mental Disorders
Contraceptive Agents, Female
Depression
Behavioral Symptoms
Estradiol
Polyestradiol phosphate
Estrogens
Progesterone
Estradiol valerate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses
Progestins

ClinicalTrials.gov processed this record on July 20, 2014