Daily Stress and Vascular Function in Midlife as a Risk Factor for Cognitive Decline

NCT06466655 | Completed Results

• 2 other identifiers: 20567842P20GM113125
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this pilot clinical trial is to begin to understand how day-to-day stress affects cardiovascular health and brain function in middle-aged adults. The main question aims to answer is whether the link between daily stress and vascular dysfunction is a potential mechanism of increased risk for future cognitive decline. Participants will complete a 15-day testing cycle. During this cycle, participants will complete daily assessments of stress using an online survey tool for 14-consecutive days. On the last day of each cycle, vascular function will be assessed during a laboratory visit.

Conditions

Middle-aged Adults; Major Depressive Disorder

Keywords

intradermal microdialysis; microvascular function; endothelium-dependent dilation; nitric oxide; stress; cognitive function

Outcome Measures

Primary Outcomes (1)

• Nitric Oxide (NO)-Mediated Endothelium-dependent Dilation (EDD)

  NO-mediated EDD will be calculated as the relative difference (%) in dilation from the local heating-induced plateau to the post-L-NAME plateau after scavenging mitochondrial-derived superoxide

  Day 15 following a standard local heating protocol, an average of 4 hours during the 15-day cycle

Secondary Outcomes (1)

• Local Heating-induced Endothelium-dependent Dilation (EDD)

  Day 15 following a standard local heating protocol, an average of 4 hours during the 15-day cycle

Study Arms (2)

middle-aged healthy adults

ACTIVE COMPARATOR

middle-aged healthy adults

Drug: MitoTempol; Drug: Lactated Ringer's (control)

middle-aged adults with major depressive disorder

EXPERIMENTAL

middle-aged adults with major depressive disorder

Drug: MitoTempol; Drug: Lactated Ringer's (control)

Interventions

MitoTempol DRUG

One intradermal microdialysis probes will be perfused with MitoTempol (0.5 mM) during a standard local skin heating protocol.

middle-aged adults with major depressive disorder; middle-aged healthy adults

Lactated Ringer's (control) DRUG

One intradermal microdialysis probes will be perfused with lactated Ringer's (control) during a standard local skin heating protocol.

middle-aged adults with major depressive disorder; middle-aged healthy adults

Eligibility Criteria

• Age: 40 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females aged 40-55 yrs
• Absence of objective cognitive impairment (≥26 on the Montreal Cognitive Assessment)
• Absence of diagnosed or unstable neurocognitive, cardiovascular, metabolic, renal, hepatic, autonomic, autoimmune, or dermatological diseases, as determined by medical history, physical examination, blood chemistries, and 12-lead resting electrocardiogram
• 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:
• \<40 or \>55 yrs
• Psychiatric illness aside from MDD (e.g., bipolar disorder, schizophrenia, eating disorders), assessed by the MINI and self-report
• Objective cognitive impairment (\<26 on the Montreal Cognitive Assessment)
• Diagnosed or unstable neurocognitive, cardiovascular, metabolic, renal, hepatic, autonomic, autoimmune, or dermatological diseases
• Current or recent use (within 8 wks) of medications that alter cardiovascular function or psychoactive/psychopharmacological drugs
• Body mass index ≥35 kg/m2
• Resting systolic BP ≥140 mmHg
• HbA1c ≥5.7%
• Direct low-density lipoprotein ≥160mg/dl
• 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

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Ringer's Lactate

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Jody Greaney, PhD
• Organization: University of Delaware

jgreaney@udel.edu

3028312193

Study Officials

• Jody Greaney, PhD

  University of Delaware

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: June 4, 2024
• First Posted: June 20, 2024
• Study Start: May 30, 2024
• Primary Completion: April 10, 2025
• Study Completion: May 29, 2025
• Last Updated: October 2, 2025
• Results First Posted: October 2, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: Analysis scripts will shared at the time of the associated publication.

Locations

US (1)