Recovery, Fatigability, and Proteomic Response to Aerobic Exercise Training in Healthy Individuals
Condition: Adult; Fatigue
MeSH terms: Fatigue
Study type: Interventional

Summary: 
      The purpose of this protocol is to investigate the role of expired non-metabolic carbon
      dioxide in the relationship between fatigability and recovery and the response to aerobic
      exercise training in healthy individuals. Both fatigability and recovery are profoundly
      influenced by mitochondrial energetics which can be inhibited by ionic by-product
      accumulation during exercise. Buffering mechanisms of these fatigue-inducing ions releases
      non-metabolic carbon dioxide (CO2) that can be measured as expired CO2 (VCO2) during
      cardiopulmonary exercise testing (CPET), however the role of non-metabolic VCO2 in the
      relationship between fatigability and recovery has yet to be investigated.

      Furthermore, this study aims to identify the how the patterns of proteins in healthy
      individuals respond to aerobic exercise training (e.g. stationary cycling) over approximately
      one month. The underlying mechanisms of recovery after physical activity, including
      mechanisms or biological pathways that could be highlighted by analysis of proteins in urine,
      could add to scientific knowledge regarding physical activity tolerance and potential
      exercise interventions. This knowledge could eventually assist with designing precise and
      personalized exercise interventions to improve physical activity performance.

      The investigators hypothesize that 1) non-metabolic CO2 will be at least moderately
      associated with the inverse relationship between fatigability and recovery; and 2) highly
      active adults, compared to sedentary individuals, will exhibit differential proteomic
      patterns in response to an initial acute bout and subsequent repeated bouts of aerobic
      exercise.
    

Detailed description: 
      Subjects will be recruited from the greater Washington D.C. metro area by word of mouth,
      university classes, healthcare provider referral, social media posting, and by posted fliers.
      Healthy males and females as determined by the Physical Activity Readiness Questionnaire Plus
      (PARQ+) will qualify to participate, regardless of their fitness level. The study design and
      participation will be explained to those who are potentially interested in participating in
      the study. Individuals interested in participating as subjects will complete the PARQ+ and
      those answering "no" to all of the PARQ+ questions will qualify for inclusion. Those
      answering "yes" to one or more of the questions will be asked follow-up questions to
      determine if they meet inclusion/exclusion criteria. Subjects will then be consented and
      enrolled for participation.

      Visit 1: Subjects meeting all inclusion criteria and no exclusion criterion will be consented
      and enrolled in the study. Subjects will then complete the International Physical Activity
      Questionnaire (IPAQ) to describe their current levels of physical activity. Height and weight
      measurements of the subject will also be taken. Subjects will then complete a standard peak
      cardiopulmonary exercise test (pkCPET) to volitional exhaustion with near infrared
      spectroscopy (NIRS) assessment of muscle oxygenation and microvascular reactivity,
      bioimpedance cardiographic (ZCG) assessment of cardiac output and stroke volume, and
      electrocardiographic (EKG) measurement of heart rate (HR) at rest and during exercise. After
      a 10-minute passive recovery period, subjects will perform an endurance based CPET (enCPET)
      at intensity of 70% of the peak wattage reached during the pkCPET, again to volitional
      exhaustion followed by a final 10-minute passive recovery period to conclude day one of
      testing.

      Visit 2: Subjects will complete a submaximal square-wave test (swCPET) for measurement of
      oxygen on-kinetics. After a 10-minute recovery period, subjects will complete the same enCPET
      they performed during Visit 1 testing. This testing will again be followed by a 10-minute
      recovery period. EKG measurements of HR will be taken during exercise and rest periods.
      Subjects will receive a urine collection cup to be used prior to visit 3. Subjects will be
      asked to collect approximately 75-90 mL of urine on the morning of Visit 3 to provide upon
      arrival. Subjects will be asked to log food intake using the form described below for 48
      hours, starting 24 hours prior to Visit 3.

      Visits 3-19: On days 3-19, subjects will complete a continuous high intensity aerobic
      exercise training (AET) protocol. Subjects will warm up for approximately 5-minutes, exercise
      within their predetermined HR range for 45 minutes, followed by a 5-10 min recovery period.
      HR will be monitored using a Polar chest strap worn by the subject and a paired watch and the
      heart rate reading on the cycle ergometer monitored by the investigators. The entire training
      session will take approximately 60 minutes. Following Visit 3, subjects will be provided with
      a 2nd urine sample cup and asked to collect a "first-morning" urine sample (75-90mL) at home
      on the day after visit 3. Subjects will be asked to provide subsequent first-morning
      midstream urine samples at home on the morning of and the morning after visits 7, 11, 15, and
      19 (10 total urine samples). Subjects will be provided with a copy of their initial food log
      and asked to repeat their nutritional intake for the same timeframe as the initial sample for
      each subsequent sample (24 hours prior to pre-exercise sample until post-exercise sample).

      Visit 20: Subjects will repeat the same procedures performed at Visit 1 including a pkCPET,
      10-minute recovery, enCPET, 10-minute recovery, in that order. NIRS, ZCG, and EKG again will
      be collected throughout both the active and recovery portions of the testing.

      Visit 21: Subjects will repeat the same procedures performed on day two of testing including
      a swCPET, 10-minute recovery, enCPET, 10-minute recovery, in the order. EKG data will again
      be collected during the active and recovery portions of the testing.
    

Intervention name(s): Aerobic Exercise Training
Intervention type(s): Other
Intervention description(s): see arm/group description
Intervention model: Single Group Assignment
Intervention model description: One arm, a single group of healthy individuals, will perform cardiopulmonary exercise testing pre and post an aerobic exercise training program.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: recovery; proteomics; cardiorespiratory fitness; exercise; aerobic exercise training