Probing the Role of Mitochondrial Oxidative Stress in Impaired Vascular Function Among Young Adults With Early Life Adversity

NCT07244809 | Recruiting

• 1 other identifier: 202504919
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Adverse childhood experiences (ACEs) represent highly stressful events in the first 18 years of life that include abuse, neglect, and household and community-level dysfunction. Greater exposure to ACEs are associated with greater increases in the risk of cardiovascular diseases and death. Our laboratory has previously observed that vascular function is disrupted in young adults with prior ACE exposure, even though these individuals appear to be healthy clinically (i.e., no classic clinical cardiovascular disease risk factors). There is a need to identify and understand the biological mechanisms underlying these vascular impairments to inform effective interventions to reduce cardiovascular risks the millions of individuals affected by ACEs. The body's response to stress is coordinated across various systems, all of which depend on energy supplied by mitochondria (often referred to as the "powerhouse of cells"). Based on new evidence across multiple physiological systems from our team, our overarching hypothesis is that disruption of mitochondrial function contributes to cardiovascular impairments among young adults with ACEs. Here we propose the initial pilot work necessary to begin to understand these associations, which will directly inform identification of individuals who may be most vulnerable to stress-related cardiovascular risk and the development of interventions to promote cardiovascular-stress resilience. Our aims are to:

1. 1.Determine whether mitochondrial oxidative stress contributes to impaired vascular function among young adults who experienced early life adversity.
2. 2.Determine whether reducing mitochondrial oxidative stress improves the cellular stress and integrated cardiovascular response to laboratory-based psychosocial stress among young adults who experienced early life adversity.

Conditions

Adverse Childhood Experience; Endothelial Function (FMD); Endothelial Injury; Mitochondrial Function; Oxidative Stress; Psychosocial Influence on Cardiovascular Disease

Keywords

flow mediated dilation; mitoquinone mesylate; placebo; early life adversity; trier social stress test

Outcome Measures

Primary Outcomes (4)

• Vascular endothelial function

  Vascular endothelial function will be assessed using the brachial artery flow mediated dilation technique

  Prior to supplementation and 60 minutes after supplementation

• Blood pressure

  The blood pressure response to psychosocial stress induced by the Trier Social Stress Test will be determined using beat-to-beat blood pressure measurement by finger photoplethysmography (or brachial artery blood pressure in the case of equipment errors). The Trier Social Stress Test will be performed after post-supplementation measurement of vascular endothelial function (FMD).

  75 minutes after supplementation, during, and for 45 minutes after completion of the Trier Social Stress Test.

• Endothelial Cell Microparticle Release

  Endothelial cell microparticle release will be quantified from platelet-poor plasma in response to psychosocial stress induced by the Trier Social Stress Test. The Trier Social Stress Test will be performed after post-supplementation measurement of vascular endothelial function (FMD).

  60 minutes after supplementation and immediately following, 5-10 min, 15-20 min, and 45 min following the Trier Social Stress Test.

• Cortisol

  Cortisol will be quantified from drool collected passively to assess the HPA-axis response to psychosocial stress induced by the Trier Social Stress Test. The Trier Social Stress Test will be performed after post-supplementation measurement of vascular endothelial function (FMD).

  60 minutes after supplementation and immediately following, 5-10 min, 15-20 min, and 45 min following the Trier Social Stress Test.

Secondary Outcomes (3)

• Total Peripheral Resistance

  75 minutes after supplementation, during, and for 45 minutes after completion of the Trier Social Stress Test.

• Cardiac Output

  75 minutes after supplementation, during, and for 45 minutes after completion of the Trier Social Stress Test.

• Growth Differentiation Factor 15

  60 minutes after supplementation and immediately following, 5-10 min, 15-20 min, and 45 minutes after completion of the Trier Social Stress Test.

Study Arms (2)

Mitoquinone Mesylate (MitoQ)

EXPERIMENTAL

Mitoquinone Mesylate (160 mg, single dose)

Dietary Supplement: Mitoquinone mesylate (MitoQ)

Placebo

PLACEBO COMPARATOR

Matched placebo (microcrystalline cellulose and tapioca, 160 mg, single dose)

Dietary Supplement: Placebo

Interventions

Mitoquinone mesylate (MitoQ) DIETARY_SUPPLEMENT

Participants will consume a single 160 mg dose of mitoquinone mesylate, provided in the form of 6, 20 mg capsules, with water.

Mitoquinone Mesylate (MitoQ)

Placebo DIETARY_SUPPLEMENT

Participants will consume a single 160 mg dose of microcrystalline cellulose and tapioca (placebo), provided in 20 mg capsules, with water.

Placebo

Eligibility Criteria

• Age: 18 Years - 29 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• years
• ACE score \>=4

You may not qualify if:

• Resting arterial blood pressure \>140/90 mmHg
• BMI \<=17 or \>= 35
• Are on a weight-loss diet or involved in a formal weight-loss program or are not intentionally weight stable for 6 months (+/- 5 kg) prior to the study.
• Cardiovascular or metabolic prescription drug use
• Vasoactive antidepressant drug use (SSRIs and clonidine)
• Current heavy alcohol use, as defined as binge drinking on 5 or more days in the last month, or consuming more than 7 (women) or 14 (men) drinks per week in the last month (per NIAAA definition)
• Current or recent (within the last 6 mo.) illicit drug use disorder as indicated by a score of 3 or greater on the Drug Abuse Screening Test (DAST-10)
• Current tobacco or nicotine use
• Vaping
• Regular vigorous (\>6 METs) aerobic exercise (\>4 bouts/week, \>30 min/bout)
• dietary supplementation with antioxidants or habitual use of NSAIDs
• Currently pregnant or breastfeeding

Sponsors & Collaborators

• University of Iowa: lead
• MitoQ Limited: collaborator

Study Sites (1)

Integrative Laboratory of Applied Physiology and Lifestyle Medicine

Iowa City, Iowa, 52242, United States

RECRUITING

Related Publications (3)

• Pilgrim JA, Crawford M. Low blood pressure and wellbeing. BMJ. 1993 Mar 6;306(6878):655. doi: 10.1136/bmj.306.6878.655-a. No abstract available.

  PMID: 8461842 BACKGROUND

• Manson W, Annan WD. The structure of a phosphopeptide derived from -casein. Arch Biochem Biophys. 1971 Jul;145(1):16-26. doi: 10.1016/0003-9861(71)90004-x. No abstract available.

  PMID: 4941633 BACKGROUND

• Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, Koss MP, Marks JS. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998 May;14(4):245-58. doi: 10.1016/s0749-3797(98)00017-8.

  PMID: 9635069 BACKGROUND

MeSH Terms

Interventions

mitoquinone

Central Study Contacts

Manoela Lima Oliveria, PhD

CONTACT

(319)467-3125; manoela-limaoliveira@uiowa.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: November 24, 2025
• Study Start: October 13, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 24, 2025

Record last verified: 2025-11

Locations

US (1)