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

NCT06860724 | Recruiting

• 2 other identifiers: 2270844P20GM113125
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Major Depressive Disorder

Keywords

stress; affect; endothelial function

Outcome Measures

Primary Outcomes (2)

• Nitric oxide (NO)-mediated endothelium-dependent dilation (EDD)

  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

  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

Study Arms (2)

healthy adults

ACTIVE COMPARATOR

non-depressed healthy adults

Other: NG-nitro-L-arginine methyl ester (L-NAME)

adults with major depressive disorder

EXPERIMENTAL

adults with major depressive disorder (unmedicated)

Other: NG-nitro-L-arginine methyl ester (L-NAME)

Interventions

NG-nitro-L-arginine methyl ester (L-NAME) OTHER

Acute local perfusion of L-NAME (15 mM) directly to the microvasculature will be used to inhibit NO synthase.

adults with major depressive disorder; healthy adults

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Delaware: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

University of Delaware

Newark, Delaware, 19713, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

NG-Nitroarginine Methyl Ester

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino

Central Study Contacts

Jody Greaney, PhD

CONTACT

302-831-2193; jgreaney@udel.edu

Study Design

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

Study Record Dates

• First Submitted: February 28, 2025
• First Posted: March 6, 2025
• Study Start: January 6, 2025
• Primary Completion (Estimated): December 30, 2030
• Study Completion (Estimated): December 1, 2031
• Last Updated: September 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)