Mitochondrial DNA Signatures of Poor Aerobic Exercise Trainability in Young Adults Born Preterm

NCT06334107 | Recruiting

• 1 other identifier: 24AIREA1191995
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Young adults born very preterm (32 weeks gestation or earlier) do not respond well to aerobic exercise training, meeting the recommendations set by the Physical Activity Guidelines for Americans, where they do not increase their fitness level (or cardiorespiratory fitness). Thus, they do not receive the health benefits of exercise. Achieving physical fitness through aerobic exercise training is the most cost-effective method for preventing and treating many diseases. Young adults born very preterm also have a higher risk of these conditions. Thus, their inability to respond to increase their fitness is a major problem. One likely explanation for poor exercise trainability and increased heart disease risk in young adults born very preterm is the effect of the early birth on the major energy producers in all our cells: Mitochondria. During late-stage gestation, mitochondria change from relying on sugar as a major fuel source to fat. Unfortunately, individuals born very preterm miss this transition in fuel source reliance, which causes significant stress and damage to mitochondria. Mitochondria are critical for post-natal organ development; thus, it is thought that preterm birth-induced mitochondrial dysfunction is the underlying cause of poor trainability and high disease risk in young adults born very preterm. Indeed, mitochondrial dysfunction is evident in these individuals. To date, there is not a way to help young adults born preterm improve their fitness level. One likely target is in the mitochondria: it's DNA. Mitochondrial DNA helps determine how mitochondria function and can be damaged under stress. Our goal in this proposed work is to determine the role of mitochondrial DNA in mitochondrial dysfunction and its link to their poor trainability. Questions:

1. 1.Are there mitochondrial DNA markers linked to mitochondrial dysfunction and poor exercise trainability in young adults very born preterm?
2. 2.Do mitochondrial DNA in young adults born very preterm respond differently to aerobic exercise training than those born at term?

Conditions

Preterm Birth

Keywords

Preterm birth; Aerobic capacity trainability; mitochondrial DNA; heteroplasmy; mitochondrial oxidative capacity

Outcome Measures

Primary Outcomes (4)

• Mitochondrial DNA heteroplasmy

  The full-length mitochondrial DNA sequence will be analyzed and assessed for heteroplasmic sites in the mitochondrial genome. Briefly, mitochondrial DNA exists in many copies, and heteroplasmy is noted when the amino acid sequence changes from the major read 2% or more across the DNA copies. The change in the mean heteroplasmy frequency and the mean number of sites with heteroplasmy with aerobic exercise training by comparing these changes in young adults born preterm to those born at term.

  Immediately after aerobic exercise training intervention; change in pre- to post-frequency

• Mitochondrial DNA sequence variants

  The full-length mitochondrial DNA sequence will be determined in participants who report being born prematurely, which will be compared to their biological birth mother. In this comparison, we will assess for variants. We deem a site as an 'informative' mitochondrial DNA variant in young adults born prematurely as a change in amino acid sequence from the biological birth mother.

  Immediately after visit 1

• Change in maximal aerobic capacity

  The change in maximal aerobic capacity will be assessed via the modified Balke-graded exercise test before and after the aerobic exercise training program.

  Immediately after aerobic exercise training intervention; change in pre- to post-frequency

• Change in mitochondrial oxidative capacity in peripheral blood mononuclear cells

  Mitochondrial maximal respiration (i.e., oxidative capacity) will be measured in isolated peripheral blood mononuclear cells.

  Immediately after aerobic exercise training intervention; change in pre- to post-frequency

Secondary Outcomes (1)

• Daily sleep habits

  Daily for 16 weeks.

Study Arms (2)

Aerobic Exercise Training

EXPERIMENTAL

Participants will be asked to complete a 16-week aerobic exercise training program.

Behavioral: Exercise

Mitochondrial DNA Sequencing

NO INTERVENTION

Participants will be asked to provide a blood or saliva sample for mitochondrial DNA sequencing analysis to assess for variants unique to individuals born prematurely.

Interventions

Exercise BEHAVIORAL

Participants will be asked to follow a moderate-intensity aerobic exercise training program for 4-5 days per week for 40-60 minutes each session.

Aerobic Exercise Training

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Preterm born (PTB)young adult group: Participants must be inactive (reported exercise \< 150 mins/week; See IPAQ Attachment), males and females aged 18-35 years born preterm with a gestational age \<37 weeks.
• Normal term-born (NTB) young adult control group: Participants must be inactive (reported exercise \< 150 mins/week) and will be age- and sex-matched and born at term (37 gestational age).
• The biological mother of PTB participants: The PTB biological birth mother must be the one who gave birth to the participant and the one from whom the child inherited half of its genetic background (i.e., DNA).
• PTB and NTB young adults must pass the PAR-Q+ Questionnaire assessment, indicating readiness to begin a moderate-intensity exercise training program. We will follow the American College of Sports Medicine\'s aerobic exercise training program participation guidelines. Subjects who are cleared via the PAR-Q+ assessment will be permitted to participate in the training program.

You may not qualify if:

• PTB and NTB young adults only: Having a diagnosed bronchopulmonary hyperplasia, cardiovascular (cardiac or peripheral arterial disease), metabolic (Diabetes Mellitus Type 1 or 2), or renal or liver disease, and signs or symptoms of these conditions, including pain: discomfort in the chest, neck, jaw, arms, or other areas that may result from ischemia; shortness of breath at rest or with mild exertion; dizziness or syncope; orthopnea or paroxysmal nocturnal dyspnea; ankle edema; palpitations or tachycardia; intermittent claudication; known heart murmur; unusual fatigue or shortness of breath with usual activity.

Sponsors & Collaborators

• Texas Tech University: lead

Study Sites (1)

Texas Tech University | Kinesiology and Sport Management Building

Lubbock, Texas, 79409, United States

RECRUITING

MeSH Terms

Conditions

Premature Birth

Interventions

Exercise

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Heather L Vellers, Ph.D.

CONTACT

8068348554; heather.l.vellers@ttu.edu

Heather L Vellers, Ph.D.

CONTACT

9792194343; heather.l.vellers@ttu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: March 27, 2024
• Study Start: May 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)