Stress Testing for Heart Disease

(DASHH Trial)

Overseen By Margo Nathan, MD

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Hormonal agents, Steroids, Antihistamines, others

Disqualifiers: Bipolar, Psychotic disorder, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 1 day

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand why women experiencing depression during menopause might face a higher risk of heart disease. Researchers are examining two stress-related systems in the body to explore their potential connection to depression and heart health. Women in perimenopause, with or without depression, will participate in the Trier Social Stress Test (TSST) to gather insights. Women who have had irregular periods for at least 60 days but less than a year and are not taking certain medications or using nicotine may be suitable for this study. As an unphased trial, this study offers a unique opportunity to contribute to understanding the link between menopause, depression, and heart health.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as hormonal agents, steroids, blood pressure medications, and antihistamines, for a specific period before participating. However, you can continue taking antidepressant medications if your dose has been stable for at least 30 days before the study.

What prior data suggests that this stress testing method is safe for women?

Research shows that the Trier Social Stress Test (TSST) is generally manageable for participants. Although it can cause temporary stress, it does not lead to lasting negative effects. Researchers often use this test to study the impact of stress on the body and mind. Studies have found that participants might experience a faster heartbeat and higher stress hormone levels, but these changes are normal and subside quickly after the test. Overall, the TSST is considered safe, and studies using this method have reported no serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Trier Social Stress Test (TSST) because it explores the relationship between social stress and heart disease, particularly in women with and without perimenopausal depression. Unlike standard diagnostic methods for heart disease, which typically involve physical stress testing or imaging, TSST involves a controlled social stressor to observe its impact on heart health. This approach could lead to new insights into how stress uniquely affects women during the perimenopausal phase, potentially guiding more personalized strategies for preventing heart disease in this group.

What evidence suggests that the Trier Social Stress Test is effective for studying stress pathways in perimenopausal women?

Research has shown that the Trier Social Stress Test (TSST) effectively triggers stress reactions, such as changes in heart rate and blood pressure. These reactions help researchers understand how stress affects the body, particularly in women undergoing perimenopause, a period when they are more prone to depression and heart disease. In this trial, participants will undergo the TSST to study these effects. Studies have found that problems with the body's stress response system, known as the hypothalamic-pituitary-adrenal axis (HPAA), link to various mental health issues. By studying these stress pathways, researchers might discover how depression during perimenopause could increase the risk of heart disease in women. Understanding these connections can help develop strategies to reduce this risk and improve health. ^{1 2 4 6 7}

Who Is on the Research Team?

Margo Nathan, MD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

This study is for women aged 44-55 in late perimenopause, who may be on stable antidepressant medication. It's not for those with severe depression, current CVD or diabetes, recent use of certain blood pressure or steroid medications, active smoking or substance abuse, or hormonal treatments within the last month.

Inclusion Criteria

You have taken antihistamines in the last two weeks.

I am a woman aged 44-55 and am in the late stage of transitioning to menopause.

My antidepressant dose has been stable for the last 30 days.

Exclusion Criteria

I am taking or have recently taken medications that affect my RAAS.

I have taken blood pressure medication in the last 3 months.

You currently have a problem with drinking alcohol or using drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (remote)

Treatment

Participants undergo a social stress task (TSST) and physiological measurements are taken

1 day

1 visit (in-person)

Follow-up

Participants have a brief telephone call to review participation and answer questions

1 day

1 visit (telephone)

What Are the Treatments Tested in This Trial?

Interventions

• Trier Social Stress Test

Trial Overview

The trial explores how stress affects heart health and depression during menopause by testing responses to the Trier Social Stress Test. It aims to understand if disruptions in stress pathways contribute to cardiovascular disease risk in midlife women.

How Is the Trial Designed?

Group I: Women without perimenopausal depression Experimental Treatment 1 Intervention

Participants will undergo a social stress task (TSST)

Group II: Women with perimenopausal depression Experimental Treatment 1 Intervention

Participants will undergo a social stress task (TSST)

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

The Foundation of Hope for Research and Treatment of Mental Illness

Collaborator

Trials

3

Recruited

50+

Published Research Related to This Trial

The study utilized the Trier Social Stress Test (TSST) to analyze both non-verbal and verbal communication behaviors, identifying 51 distinct behavioral sequences that illustrate the complexity of human communication under stress.

Using T-Pattern Analysis, the research revealed that non-verbal and verbal behaviors interact in a structured manner during the TSST, emphasizing the importance of multimodal communication in understanding stress responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurring sequences of multimodal non-verbal and verbal communication during a human psycho-social stress test: A temporal pattern analysis. Santangelo, A., Monteleone, AM., Casarrubea, M., et al.[2021]

The virtual version of the Trier Social Stress Test (TSST) effectively induced a significant acute stress response in 50 undergraduate students, as evidenced by increased cortisol levels and subjective stress reports.

This virtual approach may offer advantages such as reduced costs and greater accessibility for psychological experiments, while also revealing that individuals who recently experienced loss had a dampened cortisol response, aligning with previous research findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of a Virtual Trier Social Stress Test: Initial Findings and Benchmarking Comparisons. Fallon, MA., Careaga, JS., Sbarra, DA., et al.[2018]

The study validated a remote version of the Trier Social Stress Test (TSST-Online) for children, demonstrating that it effectively activates the stress response similar to in-person assessments, with 63% of participants showing a significant increase in cortisol levels.

The TSST-Online allows for safe and effective assessment of stress reactivity in children and adolescents without the need for in-person visits, making it particularly useful during situations like the COVID-19 pandemic or for participants living far from research facilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of an online version of the Trier Social Stress Test in a study of adolescents. Gunnar, MR., Reid, BM., Donzella, B., et al.[2023]

The remote Trier Social Stress Test (rTSST) effectively elicited negative affect and increased cardiovascular responses (like heart rate) in participants under stress compared to a control group, indicating its efficacy in simulating stress responses.

The rTSST demonstrated good test-retest reliability for cardiovascular responses when assessed one week later, suggesting it can be a reliable tool for future research on stress and its effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An online Trier social stress paradigm to evoke affective and cardiovascular responses. DuPont, CM., Pressman, SD., Reed, RG., et al.[2022]

The Trier Social Stress Test in group format (TSST-G) effectively induces a psychobiological stress response, as shown by significant increases in negative affect, heart rate (HR), and salivary alpha-amylase (sAA) in a study with 294 participants during the first test.

When comparing two different protocols for the second test, the defensive speech protocol resulted in a stronger autonomic stress response (higher HR and lower heart rate variability) than a neutral presentation, indicating that ego-involving tasks may be more effective for studying stress reactivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mood and autonomic responses to repeated exposure to the Trier Social Stress Test for Groups (TSST-G). Boesch, M., Sefidan, S., Ehlert, U., et al.[2014]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05570721

Depression, Aging, Stress and Heart Health Study (DASHH)

Findings will provide important insight into potential mechanisms by which depression during perimenopause may increase risk for CVD in midlife women, which ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7739033/

A systematic review of the Trier Social Stress Test methodology

Importantly, researchers have demonstrated that dysfunctional HPAA activation is associated with various mental health conditions (Wingenfeld and Wolf, 2010).

3.

withpower.com

withpower.com/trial/phase-stress-psychology-9-2022-425a4

Stress Testing for Heart Disease (DASHH Trial)

The Trier Social Stress Test (TSST) has been shown to effectively induce stress responses, including changes in heart rate and blood pressure, which are ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01308814

Perimenopausal Estrogen Replacement Therapy Study

The primary objective of this study is to examine the prophylactic role of estradiol in the development of depressive symptoms and the progression of ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9716440/

Baseline anxiety-sensitivity to estradiol fluctuations predicts ...

The menopausal transition (perimenopause) is associated with an increased risk of major depression, characterized by anxiety and anhedonia ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/32706883/

IL-6 Response to Psychosocial Stress Predicts 12-month ...

Greater baseline IL-6 levels as well as its reactivity to stress may predict worsening in distinct cardiometabolic biomarkers as women transition to menopause.

7.

researchgate.net

researchgate.net/publication/343201623_IL-6_Response_to_Psychosocial_Stress_Predicts_12-month_Changes_in_Cardiometabolic_Biomarkers_in_Perimenopausal_Women

IL-6 Response to Psychosocial Stress Predicts 12-month ...

At study onset, participants underwent the Trier Social Stress Test (TSST), and plasma IL-6 was measured repeatedly before and during the one hour post-TSST.