Intermittent Hypoxia and Balance Control
Condition: Intermittent Hypoxia; Normoxia
MeSH terms: Hypoxia
Study type: Interventional

Summary: 
      This study aims to determine the effect of acute mild intermittent hypoxia on ankle
      plantarflexor muscle output during balance regulation and walking in younger and older
      adults. Fifteen younger adults and 15 older adults will be recruited to participate in the
      cross-over design study that requires 2 visits (at least 1-week apart). Participants will be
      pseudo-randomly assigned to receive either intermittent hypoxia or sham during the first
      visit, and then switch over to receive sham or intermittent hypoxia during the 2nd visit.
      Muscle activation patterns and kinetic and kinematics during standing and walking will be
      recorded before and after the intermittent hypoxia/sham. It is hypothesized that compared to
      the sham condition, both younger and older participants will show greater increases in ankle
      plantarflexor muscle activation during gait and balance assessments following intermittent
      hypoxia.
    

Detailed description: 
      Procedure:

      This is a cross-over design study that requires 2 visits (at least 1-week apart). Fifteen
      younger adults and 15 older adults will be recruited. Participants will be pseudo-randomly
      assigned to receive either intermittent hypoxia or sham during the first visit, and then
      switch over to receive sham or intermittent hypoxia during the 2nd visit.

      During each visit, participants will first perform Gait and Balance Assessments (PRE),
      followed by the Intermittent Hypoxia (or sham) protocol, and then perform Gait and Balance
      Assessments (POST) again. The total time is approximately 2.5 hours for each visit.

      Balance and Gait Assessments The consent process and Balance and Gait Assessments will take
      place in BEL 530.

      During Balance and Gait Assessments, participants will be asked to wear tight-fitting shorts
      and shirt for accurate marker positioning. Approximately 39 reflective markers will be
      attached to target locations on the individuals' body (the head, arms, wrists, hands, trunk,
      pelvis, legs and feet) according to the Vicon Full-Body Plug-In Gait Model.

      A study team member will attach surface electrodes over the tibialis anterior and soleus
      muscles to record the muscle activation patterns with a wireless Electromyography (EMG)
      system (Delsys Inc., Natick, MA). Next, a study team member will assist the participant to
      wear a safety harness that will be attached to an overhead support beam.

      For Balance Assessment, participants will stand on the treadmill with their feet
      shoulder-width apart. A 30-second quiet standing trial will be recorded. Next, participants
      will be instructed to maintain upright posture when the treadmill shifts forward or backward
      at unknown times (perturbed standing). The treadmill will shift approximately 3 cm. Based on
      our previous experiment, this distance is sufficient to trigger a response without inducing a
      fall. Three forward and 3 backward treadmill shifts will be delivered in a randomized order.
      Finally, participants will be asked to close their eyes and repeat the quiet standing and
      perturbed standing trials. A 10-camera Vicon Nexus motion capture system (Vicon, Oxford
      Metrics, UK) will be used to record whole body kinematics. Ground reaction forces under each
      belt will be recorded. A handrail is located on either side of the treadmill.

      For Gait Assessments, participants will walk on the treadmill at their comfortable and fast
      walking speeds. The comfortable speed will be determined by gradually increasing the
      treadmill speed until the participant confirms that it reaches their comfortable regular
      walking speed. The fast speed will be determined by gradually increasing the treadmill speed
      until the participant confirms that it reaches the maximum speed that they can walk safely. A
      30-second walking trial will be recorded for each speed.

      Following Balance and Gait Assessment, a testing team member will escort the participant to
      BEL819 Clinical Exercise Physiology Laboratory to perform Intermittent Hypoxia (or sham).

      Intermittent hypoxia Intermittent hypoxia will be performed in BEL819 Clinical Exercise
      Physiology Laboratory. Intermittent hypoxia is routinely performed in this laboratory (IRB
      protocols 2017090015, 2018110129, 2019070088, and 202005018). Intermittent hypoxia consisting
      of a limited number (5-10/day) of short (4-10 min) bouts of mild hypoxia (oxygen levels
      between 10-12%) leads to cumulative and sustained beneficial physiological responses.
      Preliminary data collected in the Clinical Exercise Physiology Laboratory show that a
      fraction of oxygen of 11±1% corresponds to an arterial oxygen saturation of 80±2% in
      middle-aged individuals. Participants will be sitting during the entire breathing protocol.
      Hypoxic air will be inhaled through a mask connected to a two-way non-rebreathing valve,
      which will itself be connected to a 5-liter non-diffusing gas bag (Hans Rudolph, Inc, USA).
      The rebreathing bag will be connected to a certified medical grade gas tank containing 11%
      oxygen and a balance of nitrogen. The intermittent hypoxia protocol will consist of eight
      4-min cycles of breathing hypoxic air interspersed with normoxic cycles breathing room air.
      After four min of hypoxia, participants will be switched back to breathing room air until
      resaturation, which takes approximately one minute. Once arterial oxygen saturation reaches
      baseline levels, participants will be switched back to breathing hypoxic air, beginning the
      next hypoxic cycle. Unlike chronic hypoxic exposure, risks associated with an acute hypoxic
      exposure of three 4-min cycles are minimal, and no adverse events were reported during
      intermittent hypoxia in our participants.

      During the sham condition, compressed air (21% oxygen) from a gas tank will be delivered
      throughout the protocol instead of 11% oxygen. Participants will not receive information
      about which condition (Intermittent hypoxia or sham) they are experiencing during the trials.

      Pulmonary gas exchange Breath-by-breath measures of pulmonary gas exchange such as volume of
      oxygen and carbon dioxide, respiratory rate, tidal volume, minute ventilation and fraction of
      inspired oxygen will be determined from a pneumotachometer (Ultima Cardio2, MGC Diagnostics,
      MN, USA) throughout the intermittent hypoxia. The pneumotachometer will be mounted between
      the mask and the non-rebreathing valve of the breathing circuit. The pneumotachometer,
      mouthpiece and non-rebreathing valve will be disinfected in a 10% bleach and water solution
      for 60 minutes and rinse thoroughly with tap water for 5 minutes between each use. Each
      participant will have a face mask that will only be used by him/her.

      Hemodynamics An arterial waveform obtained by finger plethysmography from the middle finger
      of the left hand will be continuously recorded (NOVA, Finapres Medical Systems, Amsterdam,
      Netherlands) during the intermittent hypoxia. Systolic, diastolic and mean arterial pressure,
      heart rate, stroke volume, cardiac output and total peripheral resistance will be derived
      from the arterial waveform, a method which has been validated against invasive measures [9].
      All data will be recorded in LabChart (Powerlab, ADInstruments Inc., CO, USA) for later
      analysis.

      Arterial oxygen saturation Arterial oxygen saturation will continuously be monitored by pulse
      oximetry (NOVA, Finapres Medical Systems, Amsterdam, Netherlands) throughout the intermittent
      hypoxia. The pulse oximeter probe will be applied to the index finger of the left hand.

      Following intermittent hypoxia (or sham), a testing team member will escort the participant
      back to BEL530 to perform Balance and Gait Assessment. After the assessment, a testing team
      member will remove the electrodes and markers from the participant.
    

Intervention name(s): Intermittent Hypoxia; Normoxia (sham)
Intervention type(s): Behavioral; Behavioral
Intervention description(s): During the intermittent hypoxia session, participants will be sitting during the entire breathing protocol. Hypoxic air will be inhaled through a mask connected to a two-way non-rebreathing valve, which will itself be connected to a 5-liter non-diffusing gas bag (Hans Rudolph, Inc, USA). The rebreathing bag will be connected to a certified medical grade gas tank containing 11% oxygen and a balance of nitrogen. The intermittent hypoxia protocol will consist of eight 4-min cycles of breathing hypoxic air interspersed with normoxic cycles breathing room air. After four min of hypoxia, participants will be switched back to breathing room air until resaturation, which takes approximately one minute. Once arterial oxygen saturation reaches baseline levels, participants will be switched back to breathing hypoxic air, beginning the next hypoxic cycle.; During the sham condition, compressed air (21% oxygen) from a gas tank will be delivered throughout the protocol instead of 11% oxygen. Participants will not receive information about which condition (Intermittent hypoxia or sham) they are experiencing during the trials.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is a cross-over design study that requires 2 visits (a least 1-week apart). Fifteen younger adults and 15 older adults will be recruited. Participants will be pseudo-randomly assigned to receive either intermittent hypoxia or sham during the first visit, and then switch over to receive sham or intermittent hypoxia during the 2nd visit.
Masking: Single (Participant)
Primary purpose: Treatment