Recruiting

Observational Study

Sponsor:

University of North Carolina, Chapel Hill

Code:

NCT05570721

Conditions

Menopause

Depression

Heart Disease in Women

Stress

Eligibility Criteria

Sex: Female

Age: 44 - 55

Healthy Volunteers: Accepted

Interventions

Trier Social Stress Test

Study Details

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

Heart Disease in Women

Stress

Study ID

NCT05570721

Start date

Nov 16, 2022

Status verified date

Dec, 2025

Completion date

Jun 30, 2026

Anticipated

Primary completion date

Jun 30, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 44 - 55

Healthy Volunteers: Accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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:

1. Hormonal agents (e.g., hormone replacement therapy or combined oral contraceptive pills)within the past 30 days
2. Oral, inhaled, or injected steroids within the past 90 days
3. Blood pressure medications (e.g., Angiotensin-Converting Enzyme (ACE) inhibitors) within the past 90 days
4. Antihistamines within the past two weeks
5. 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

Study Design

Enrollment

30 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: Women with perimenopausal depression

Participants will undergo a social stress task (TSST)

experimental: Women without perimenopausal depression

Participants will undergo a social stress task (TSST)

Interventions

Trier Social Stress Test

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.

Primary outcome measure

  • Salivary aldosterone (pg/mL) levels at rest (before the stress task). [ Time Frame: Immediately prior to the stress task. ]
  • Change in salivary aldosterone (pg/mL) levels in response to the stress task. [ Time Frame: 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). [ Time Frame: Immediately prior to the stress task. ]
  • Change in plasma aldosterone (pg/mL) levels in response to the stress task. [ Time Frame: Immediately prior to and at 0 minutes after the stress task. ]
  • Plasma angiotensin II (pg/mL) levels at rest (before the stress task). [ Time Frame: Immediately prior to the stress task. ]
  • Change in plasma angiotensin II (pg/mL) levels in response to the stress task. [ Time Frame: Immediately prior to and at 0 minutes after the stress task. ]
  • Plasma renin (pg/mL/hr) levels at rest (before the stress task). [ Time Frame: Immediately prior to the stress task. ]
  • Change in plasma renin (pg/mL/hr) levels in response to the stress task [ Time Frame: Immediately prior to and at 0 minutes after the stress task ]

Central Contacts and Locations

Central contacts

Margo Nathan, MD

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

Locations

University of North Carolina at Chapel Hill

Recruiting

Chapel Hill, North Carolina, United States, 27514

Contacts

Margo Nathan

margo_nathan@med.unc.edu

margo_nathan@med.unc.edu

Principal Investigator:

Margo Nathan, MD

More Information

Sponsor

University of North Carolina, Chapel Hill

Last update posted

Dec 22, 2025

Last verified

Dec, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of North Carolina, Chapel Hill on 2025-12-22.