Mitochondrial DNA Signatures of Poor Aerobic Exercise Trainability in Young Adults Born Preterm
ConditionPreterm Birth
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-35
SponsorTexas Tech University
About this trial
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. Are there mitochondrial DNA markers linked to mitochondrial dysfunction and poor exercise trainability in young adults very born preterm? 2. Do mitochondrial DNA in young adults born very preterm respond differently to aerobic exercise training than those born at term?
The investigators expect this work will show mitochondrial DNA changes linked to mitochondrial dysfunction and poor trainability, which can be used for future targets to improve health. This work supports AHA mission by helping to identify a marker in individuals born very preterm linked to their higher heart disease risk and death early in life.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
None
Trial design
Design model
Parallel
Treatments tested in this trial
Exercise
BehavioralParticipants will be asked to follow a moderate-intensity aerobic exercise training program for 4-5 days per week for 40-60 minutes each session.
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: Aerobic Exercise TrainingExperimental treatment 1 intervention
Group B: Mitochondrial DNA SequencingNo intervention 0 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
Immediately after aerobic exercise training intervention; change in pre- to post-frequency2
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.
Time frame
Immediately after visit 13
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.
Time frame
Immediately after aerobic exercise training intervention; change in pre- to post-frequency4
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.
Time frame
Immediately after aerobic exercise training intervention; change in pre- to post-frequencySecondary outcomes
1
Daily sleep habits
Daily sleep data will be collected from the Fitbit Charge via the Fitabase software program during the experimental period. Subjects will be instructed to create a habit of wearing their Fitbit Charge each night of the training period. At the completion of the study, the research team will collect daily sleep data that includes the estimated time spent (i.e., minutes or seconds) in each stage (awake, rapid eye movement, light, and deep).
Time frame
Daily for 16 weeks.Sponsors and contacts
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Source ClinicalTrials.gov