Linking Affective Dynamics in Response to Daily Stress to Peripheral Vascular Function in Working Age Adults

September 11, 2025 updated by: University of Delaware
The objective of this proposal is to determine whether heightened negative affective responsivity (NA-R) to daily stressors is related to blunted nitric oxide (NO)-mediated endothelium-dependent dilation (EDD) in working age adults and the extent to which this association is impacted by major depressive disorder (MDD).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Convincing evidence indicates that the deleterious impacts of psychosocial stress on emotional well-being and behavioral health are likely major contributors to excessive cardiovascular disease (CVD) risk in middle-aged and younger adults. In line with this, heightened negative affective (i.e., emotional) responsivity (NA-R) to daily stressors predicts CVD morbidity and mortality. Importantly, NA-R to daily stressors-the naturally occurring but unexpected hassles and challenges that arise out of routine everyday life (e.g., argument with a partner, pressing work deadline)-is most pronounced in 'working age adults' (18-55 yrs). Unfortunately, these effects appear further compounded in adults with major depressive disorder (MDD), an increasingly prevalent mood disorder whose core pathology is characterized by dysregulated affective dynamics. However, the physiological mechanisms linking dysregulated daily stress-related affective dynamics to poorer long-term cardiovascular health trajectories in working age adults remain incompletely understood. Our global hypothesis that affective dysregulation in response to daily stressors contributes to worsening endothelial health in working age adults, the effects of which are exacerbated in adults with MDD. Working age non-depressed healthy adults (HA) and adults with MDD (unmedicated) will participate. Multiple dynamic aspects of affective regulation and daily stress processes will be assessed during routine everyday life for 14 consecutive days (mobile app). On the days immediately before and after these ambulatory assessments, the mechanistic regulation of microvascular endothelial function will be assessed (in vivo; physiological and pharmacological approaches).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Delaware
      • Newark, Delaware, United States, 19713
        • Recruiting
        • University of Delaware
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Males and females aged 18-55 yrs
  • Non-depressed health adults (HA) will have no evidence of current or lifetime history of major psychiatric illness, assessed by the MINI and self-report and confirmed by a Licensed Clinical Psychologist
  • Adults with major depressive disorder (MDD) must meet the DSM-5 criteria for MDD and be currently symptomatic, assessed by the MINI and confirmed by a Licensed Clinical Psychologist; participants with co-morbid anxiety, stress, and trauma-related disorders will be included
  • Absence of unstable or chronic clinical disease, including cardiovascular, metabolic, renal, hepatic, autonomic, autoimmune, or dermatological disease, as determined by medical history, physical examination, blood chemistries, and 12-lead resting electrocardiogram; however, to ensure a more generalizable sample, adults with elevated systolic BP (<130mmHg), direct low-density lipoprotein (<160mg/dl), and glucose (HbA1c <5.7%) will be included
  • Participants must have a level of understanding of the English language sufficient to provide informed consent and to agree to all tests and procedures, as well as the capacity and willingness to attend all study related visits and to comply with the study protocol

Exclusion Criteria:

Subjects will be excluded at the discretion of the PI/collaborating clinicians or for any of the following reasons:

  • <18 or >55 yrs
  • Lifetime or current co-morbid neuropsychiatric disease (bipolar disorder, psychotic disorders, schizophrenia, eating disorders, obsessive-compulsive disorder, alcohol or substance use disorders)
  • Serious and imminent active suicidal/homicidal ideation with intent, plans, or behaviors, determined by the Licensed Clinical Psychologist or other clinical study team staff
  • Diagnosed chronic clinical disease, including cardiovascular, metabolic, renal, hepatic, autonomic, autoimmune, or dermatological disease, as determined by medical history, physical examination (resting systolic BP ≥130mmHg, body mass index ≥35 kg/m2), clinically significant abnormal blood chemistries (direct low-density lipoprotein ≥160mg/dl, HbA1c≥5.7%), and clinically significant abnormal 12-lead resting ECG
  • Current or recent use (within last 8 wks) of medications that alter cardiovascular function or psychoactive or psychopharmacological drugs [including (but not limited to) antidepressants, antipsychotics, benzodiazepines, mood stabilizers, sedatives/hypnotics, dopaminergic agents, stimulants, buspirone, and triptans]
  • Tobacco use (including electronic cigarettes)
  • Females who are pregnant, breastfeeding, or planning to become pregnant; female subjects of child-bearing age must have a negative urine pregnancy test on the day of all experimental visits
  • Current or past use of hormone replacement therapy
  • Allergy to study drugs or pharmacological agents

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: healthy adults
non-depressed healthy adults
Other: NG-nitro-L-arginine methyl ester (L-NAME)
Acute local perfusion of L-NAME (15 mM) directly to the microvasculature will be used to inhibit NO synthase.
Experimental: adults with major depressive disorder
adults with major depressive disorder (unmedicated)
Other: NG-nitro-L-arginine methyl ester (L-NAME)
Acute local perfusion of L-NAME (15 mM) directly to the microvasculature will be used to inhibit NO synthase.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Nitric oxide (NO)-mediated endothelium-dependent dilation (EDD)
Time Frame: immediately before and after the 14-day testing cycle
A standard local heating protocol will be used to elicit EDD and the NO-dependent portion of this response will be determined pharmacologically (local perfusion of L-NAME). Vascular conductance will be calculated (CVC=flux/mean arterial pressure) and normalized to the site-specific maximum. NO-mediated EDD will be calculated as the percent change from the local heating-induced plateau to the post-L-NAME plateau.
immediately before and after the 14-day testing cycle
Negative affective responsivity (NA-R) to daily stressors
Time Frame: immediately after the 14-day testing cycle
NA-R to daily stressors will be operationalized as the within-person slope of the change in negative affect on stressor days compared to stressor-free days and calculated using multilevel modeling. The models for computing NA-R slopes will use maximum likelihood estimation (MLE), which accounts for participants potentially providing different numbers of diary days, and will include stressor exposure.
immediately after the 14-day testing cycle

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Delaware

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of General Medical Sciences (NIGMS)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 6, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 28, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 28, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 6, 2025

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 17, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 11, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2270844
  • P20GM113125 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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