Depression, Aging, Stress and Heart Health Study

NCT05570721 | Recruiting

• 1 other identifier: 22-0763
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Depression is a known risk factor for cardiovascular disease (CVD), and this comorbidity contributes significantly to the morbidity and mortality of women. The menopausal transition or perimenopause is a period of vulnerability for both depression and CVD, making it a key time to study this critical public health issue. This research will preliminarily explore whether disruption in two novel stress pathways 1) the renin-angiotensin-aldosterone system (RAAS) and autonomic nervous system (ANS) and their relationship may underlie the link between these illnesses. Findings will provide important insight into potential mechanisms by which depression during perimenopause may increase risk for CVD in midlife women, which will inform potential risk reduction and treatment strategies that can improve health outcomes in this population.

Conditions

Menopause; Depression; Stress; Heart Disease in Women

Outcome Measures

Primary Outcomes (8)

• Salivary aldosterone (pg/mL) levels at rest (before the stress task).

  Examine variability in salivary aldosterone levels (pg/mL) by calculating medians.

  Immediately prior to the stress task.

• Change in salivary aldosterone (pg/mL) levels in response to the stress task.

  Examine variability in salivary aldosterone levels (pg/mL) in response to the TSST.

  Immediately prior to the stress task and at intervals of 0, 10, and 20 minutes after the stress task.

• Plasma aldosterone (pg/mL) levels at rest (before the stress task).

  Examine variability in plasma aldosterone levels (pg/mL) by calculating medians.

  Immediately prior to the stress task.

• Change in plasma aldosterone (pg/mL) levels in response to the stress task.

  Examine variability in plasma aldosterone levels (pg/mL) in response to the TSST.

  Immediately prior to and at 0 minutes after the stress task.

• Plasma angiotensin II (pg/mL) levels at rest (before the stress task).

  Examine variability in plasma angiotensin II levels (pg/mL) by calculating medians.

  Immediately prior to the stress task.

• Change in plasma angiotensin II (pg/mL) levels in response to the stress task.

  Examine variability in plasma angiotensin II levels (pg/mL) in response to the TSST.

  Immediately prior to and at 0 minutes after the stress task.

• Plasma renin (pg/mL/hr) levels at rest (before the stress task).

  Examine variability in plasma renin levels (pg/mL/hr) by calculating medians.

  Immediately prior to the stress task.

• Change in plasma renin (pg/mL/hr) levels in response to the stress task

  Examine variability in plasma renin levels (pg/mL/hr) in response to the TSST.

  Immediately prior to and at 0 minutes after the stress task

Secondary Outcomes (2)

• Heart rate variability defined as the root mean square of successive differences (RMSSD) between normal heartbeats in ms values at rest (before the stress task).

  Epoch recorded immediately before the stress task.

• Change in heart rate variability defined as the root mean square of successive differences (RMSSD) between normal heartbeats in ms in response to the stress task.

  Epochs recorded immediately before the stress task and intervals of 0, 10, and 20 minutes after the stress task.

Study Arms (2)

Women with perimenopausal depression

EXPERIMENTAL

Participants will undergo a social stress task (TSST)

Behavioral: Trier Social Stress Test

Women without perimenopausal depression

EXPERIMENTAL

Participants will undergo a social stress task (TSST)

Behavioral: Trier Social Stress Test

Interventions

Trier Social Stress Test BEHAVIORAL

The TSST has both social-evaluative and arithmetic components. During the social-evaluative component, the participant is asked to prepare and then deliver a brief speech to the research team. After this component there is a surprise arithmetic problem. This challenge paradigm has been well-established to rapidly and robustly induce psychological stress as well as physiological indices of stress (e.g., cortisol response, heart rate response). This task takes approximately 15 minutes to complete.

Women with perimenopausal depression; Women without perimenopausal depression

Eligibility Criteria

• Age: 44 Years - 55 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women ages 44-55 in the late perimenopause reproductive phase. Perimenopausal status will be determined based on menstrual cycle history. We will enroll women who have had an interval of amenorrhea of at least 60 days but \<1 year consistent with the late menopause transition
• Participants in either group may be on antidepressant medications (for any indication), but doses must be stable within 30 days of study participation

You may not qualify if:

• History of bipolar diagnosis or primary psychotic disorder for both groups; prior history of depression in the no-perimenopausal depression group
• In the perimenopausal depression group, current depressive symptoms that are "severe" based on score of Center for Epidemiologic Studies Depression Scale (CES-D) \>25.
• Current alcohol or substance use disorder
• Current suicidal ideation with intent and history of suicide attempt within 2 years of study participation
• Current or recent use of the following medications:
• Hormonal agents (e.g., hormone replacement therapy or combined oral contraceptive pills)within the past 30 days
• Oral, inhaled, or injected steroids within the past 90 days
• Blood pressure medications (e.g., Angiotensin-Converting Enzyme (ACE) inhibitors) within the past 90 days
• Antihistamines within the past two weeks
• Other medications determined by the study team to impact the RAAS (e.g., spironolactone).
• Current cigarette or nicotine use
• Current diagnosis of cardiovascular disease, type I or II diabetes, or other medical condition which the study team determines could impact study outcomes

Sponsors & Collaborators

• The Foundation of Hope for Research and Treatment of Mental Illness: collaborator
• University of North Carolina, Chapel Hill: lead

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

RECRUITING

MeSH Terms

Conditions

Depression

Interventions

Psychological Tests

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Behavioral Disciplines and Activities

Study Officials

• Margo Nathan, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Margo Nathan, MD

CONTACT

919-962-9908; margo_nathan@med.unc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be exposed to a mental stress task (the TSST)

Study Record Dates

• First Submitted: September 27, 2022
• First Posted: October 7, 2022
• Study Start: November 16, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: beginning at 9 and continuing for 36 months following publication
• Access Criteria: Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.

Locations

US (1)