Middle-aged AdultsNCT06466655
Daily Stress and Vascular Function in Midlife as a Risk Factor for Cognitive Decline
A study testing MitoTempol in people with Middle-aged Adults and Major Depressive Disorder, run by University of Delaware at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Middle-aged Adults, Major Depressive Disorder
- What is being tested?
- MitoTempol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 30 May 2024to 29 May 2025
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Accelerated Vascular Aging in Midlife as a Mechanism Linking Daily Stress to Cognitive Decline
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.
Read the detailed description
Because of global demographic trends toward increasingly older populations, there is an urgent need to identify the mechanistic underpinnings of modifiable risk factors for age-related chronic disease risk starting in midlife in order to establish novel biological targets for therapeutic intervention strategies that can be implemented earlier in the aging trajectory and prior to clinically detectable declines in function. Major depressive disorder (MDD) is the leading cause of disability and disease burden in midlife. Accordingly, the long-term goal is to determine whether and to what extent mitochondrial reactive oxygen species (mtROS)-induced impairments in peripheral endothelium-dependent dilation (EDD) explain how daily stress impacts 'real-world' cognitive function in middle-aged adults with MDD. As a necessary first step, the objective of this pilot trial is to examine the degree to which mtROS contributes to nitric oxide-dependent EDD in middle-aged adults with major depressive disorder.
A small community sample of cognitively unimpaired middle-aged males and females with and without MDD (n=20; 40-55 yrs) will be recruited. Participants will be recruited from New Castle County, Delaware (DE) and surrounding regions and will be representative of the sex/ethnic/racial population of DE. After providing verbal and written consent, all participants will undergo a clinical exam for signs and symptoms of chronic disease by clinical nursing staff. This will include a complete health history (females will also complete a gynecological history, including a 3-mo menstrual cycle recall), physical exam (anthropometry, resting hemodynamics, and a 12-lead electrocardiogram), and basic blood biochemistry (complete blood count, lipid profile, renal function, electrolytes, HbA1c, fasting glucose and insulin).
Ambulatory Assessment Protocol (Days 1-14): Daily stress processes will be assessed each day during the last daily assessment using an adapted version of the Daily Inventory of Stressful Events (DISE; ~8 min). Daily cognitive function will be assessed in multiple domains (subjective and objective).
Laboratory Assessment of Peripheral Endothelial Function (Day 15): Microvascular endothelial function will be assessed using intradermal microdialysis coupled with laser Doppler flowmetry. Two intradermal microdialysis probes (CMA Linear 31 probe, 55 kDa) will be inserted into the dermal layer of the ventral forearm and perfused with either lactated Ringer's solution (control) or MitoTempol (0.5 mM) to scavenge mitochondrial-derived superoxide. Red cell flux will be continuously measured via integrated laser Doppler flowmeters. Mean arterial pressure will be measured via brachial auscultation every 4 min. A standard local heating protocol will be used to elicit EDD and the NO-dependent portion of this response will be determined pharmacologically, as previously described.
- Conditions
- Middle-aged Adults, Major Depressive Disorder
- Being tested
- MitoTempol, Lactated Ringer's (control)
- Keywords
- intradermal microdialysis, microvascular function, endothelium-dependent dilation, nitric oxide, stress, cognitive function
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MitoTempolDrug
One intradermal microdialysis probes will be perfused with MitoTempol (0.5 mM) during a standard local skin heating protocol.
Lactated Ringer's (control)Drug
One intradermal microdialysis probes will be perfused with lactated Ringer's (control) during a standard local skin heating protocol.
| Study group | Role | What they receive |
|---|---|---|
| middle-aged healthy adults | Active comparator | middle-aged healthy adults Receives: Drug: MitoTempol; Drug: Lactated Ringer's (control) |
| middle-aged adults with major depressive disorder | Experimental | middle-aged adults with major depressive disorder Receives: Drug: MitoTempol; Drug: Lactated Ringer's (control) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Local heating-induced EDD will be calculated as the relative difference (%) in dilation during the local heating-induced plateau compared to baseline after scavenging mitochondrial-derived superoxide
Measured: Day 15 following a standard local heating protocol, an average of 4 hours during the 15-day cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2024
- Study start30 May 2024
- Primary completion10 Apr 2025
- Study completion29 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Middle-aged AdultsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Delaware
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Sponsor
- Investigators
- Jody Greaney, PhD, Principal investigator, University of Delaware
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06466655
- Sponsor's protocol ID
- 2056784
- Other IDs
- 2P20GM113125
- Status last verified
- May 2025
- First submitted
- 4 Jun 2024
- Last updated
- 2 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Analysis scripts will be shared via the Open Science Framework.
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Accelerated Vascular Aging in Midlife as a Mechanism Linking Daily Stress to Cognitive Decline
- ClinicalTrials.gov ID
- NCT06466655
- Acronym / sponsor ID
- 2056784
- Conditions
- Middle-aged Adults, Major Depressive Disorder
- Keywords
- intradermal microdialysis, microvascular function, endothelium-dependent dilation, nitric oxide, stress, cognitive function
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of DelawareUniversity, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Study start
- 30 May 2024 (actual)
- Primary completion
- 10 Apr 2025 (actual)
- Study completion
- 29 May 2025 (actual)
- First posted
- 20 Jun 2024 (actual)
- Results
- Posted 2 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Because of global demographic trends toward increasingly older populations, there is an urgent need to identify the mechanistic underpinnings of modifiable risk factors for age-related chronic disease risk starting in midlife in order to establish novel biological targets for therapeutic intervention strategies that can be implemented earlier in the aging trajectory and prior to clinically detectable declines in function. Major depressive disorder (MDD) is the leading cause of disability and disease burden in midlife. Accordingly, the long-term goal is to determine whether and to what extent mitochondrial reactive oxygen species (mtROS)-induced impairments in peripheral endothelium-dependent dilation (EDD) explain how daily stress impacts 'real-world' cognitive function in middle-aged adults with MDD. As a necessary first step, the objective of this pilot trial is to examine the degree to which mtROS contributes to nitric oxide-dependent EDD in middle-aged adults with major depressive disorder.
A small community sample of cognitively unimpaired middle-aged males and females with and without MDD (n=20; 40-55 yrs) will be recruited. Participants will be recruited from New Castle County, Delaware (DE) and surrounding regions and will be representative of the sex/ethnic/racial population of DE. After providing verbal and written consent, all participants will undergo a clinical exam for signs and symptoms of chronic disease by clinical nursing staff. This will include a complete health history (females will also complete a gynecological history, including a 3-mo menstrual cycle recall), physical exam (anthropometry, resting hemodynamics, and a 12-lead electrocardiogram), and basic blood biochemistry (complete blood count, lipid profile, renal function, electrolytes, HbA1c, fasting glucose and insulin).
Ambulatory Assessment Protocol (Days 1-14): Daily stress processes will be assessed each day during the last daily assessment using an adapted version of the Daily Inventory of Stressful Events (DISE; ~8 min). Daily cognitive function will be assessed in multiple domains (subjective and objective).
Laboratory Assessment of Peripheral Endothelial Function (Day 15): Microvascular endothelial function will be assessed using intradermal microdialysis coupled with laser Doppler flowmetry. Two intradermal microdialysis probes (CMA Linear 31 probe, 55 kDa) will be inserted into the dermal layer of the ventral forearm and perfused with either lactated Ringer's solution (control) or MitoTempol (0.5 mM) to scavenge mitochondrial-derived superoxide. Red cell flux will be continuously measured via integrated laser Doppler flowmeters. Mean arterial pressure will be measured via brachial auscultation every 4 min. A standard local heating protocol will be used to elicit EDD and the NO-dependent portion of this response will be determined pharmacologically, as previously described.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| middle-aged healthy adults | Active comparator | Drug: MitoTempol, Drug: Lactated Ringer's (control)middle-aged healthy adults |
| middle-aged adults with major depressive disorder | Experimental | Drug: MitoTempol, Drug: Lactated Ringer's (control)middle-aged adults with major depressive disorder |
Who may qualify
- Ages
- 40 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MitoTempolOne intradermal microdialysis probes will be perfused with MitoTempol (0.5 mM) during a standard local skin heating protocol. | Drug | middle-aged adults with major depressive disorder, middle-aged healthy adults |
| Lactated Ringer's (control)One intradermal microdialysis probes will be perfused with lactated Ringer's (control) during a standard local skin heating protocol. | Drug | middle-aged adults with major depressive disorder, middle-aged healthy adults |
Primary outcome
Nitric Oxide (NO)-Mediated Endothelium-dependent Dilation (EDD)
Time frame: Day 15 following a standard local heating protocol, an average of 4 hours during the 15-day cycle
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
1 secondary outcome
Local Heating-induced Endothelium-dependent Dilation (EDD)
Time frame: Day 15 following a standard local heating protocol, an average of 4 hours during the 15-day cycle
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Analysis scripts will be shared via the Open Science Framework.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jody Greaney, PhD principal investigator
University of Delaware
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MitoTempol in people with Middle-aged Adults and Major Depressive Disorder, run by University of Delaware at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Nitric Oxide (NO)-Mediated Endothelium-dependent Dilation (EDD) (time frame: Day 15 following a standard local heating protocol, an average of 4 hours during the 15-day cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2025.