Perimenopausal Estrogen Replacement Therapy Study

Depression Clinical Trial

— PERT  

Official title:

Depression, Estrogen Replacement, and Cardiovascular Health in the Perimenopause

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01308814
• Other study ID #: 10-0542
• Secondary ID: R01MH087619
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: February 28, 2011
• Last updated: April 6, 2016
• Start date: October 2010
• Est. completion date: March 2016

Study information

• Verified date: April 2016
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 45 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Menopause
• Perimenopause

Intervention

Drug:
• Estradiol
Transdermal 17ß-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.
• 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.

Locations

Country	Name	City	State
United States	University of North Carolina	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Depressive Symptoms as Indicated by The Center for Epidemiologic Studies Depression Scale (CES-D)		Baseline, month 1, 2, 4, 6, 8, 10, 12	No
Primary	Change in Psychiatric Diagnosis as Assessed by the Structured Clinical Interview for DSM Disorders I/NP		Baseline and when prompted by CES-D score	No
Primary	Change in Stress Reactivity during Laboratory Session including Trier Social Stress Test	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.	Baseline, month 6 and 12	No
Secondary	Change in Functional Well-being as Assessed by the Medical Outcomes Study 36-item Short form (SF-36)		Baseline, month 6 and 12	No
Secondary	Change in Metabolic risk	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	Baseline, month 6 and 12	No
Secondary	Change in Flow Mediated Vasodilatation	Flow mediated vasodilatation of the brachial artery in response to reactive hyperemia using high resolution ultrasound, yielding a measure of endothelial-dependent vasodilatation.	Baseline, month 6 and 12	No
Secondary	Change in Baroreceptor sensitivity	Cardiac autonomic control via EKG measurement of HR and beat-to-beat changes in BP to assess baroreceptor sensitivity	Baseline, month 6 and 12	No