AzTrials
AzTrials

Work of BreathingPhase 4NCT07424014

The Role of Heliox in Respiratory Control

A Phase 4 study testing Heliox inspirate in people with Work of Breathing, run by Indiana University at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record

Search all trials

Trial summary

Warfighters are frequently exposed to environments and life-support systems that increase breathing resistance and the work of breathing (WOB), such as aircraft on-board oxygen generation systems and underwater breathing apparatuses. Read more about this study

Who is it for?
Ages 18 to 40 yearsHealthy volunteers can take part
Conditions the study is for
Work of Breathing
What is being tested?
Heliox inspirate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
3 Feb 2026to 31 May 2027
Phase
Phase 4

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 40 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Between the ages of 18-40 years old.
  • English speaking and reading.
  • Self-reported weekly activity of at least 120 minutes/week of high intensity exercise for the previous 2 years.
  • Normal pulmonary function assessed by a resting forced expiratory volume in 1 second over forced vital capacity (FEV1/FVC) > 75% of predicted.
  • Normal cognitive function assessed using the Montreal cognitive function test [18].
  • Body mass index (BMI) ≤ 35 kg/m2.
  • Females with a regular menstrual cycle that ranges from 21-35 days (eumenorrhea)

Who cannot join

  • History of smoking or recreational smoking, cardiovascular disease, renal disease, pulmonary disease (including asthma or exercise-induced asthma), neurological disease, and metabolic disease.
  • Are pregnant or could possibly be pregnant by self-report.
  • Are color blind.
  • Known allergy or hypersensitivity latex.
  • Take selective serotonin reuptake inhibitors, stimulant medication, antibiotics, and chronically consume pain medication (Aleve, Tylenol, etc.).
  • Resting blood pressure of > 130mmHg systolic or 90 mmHg diastolic and/or resting pulse rate of > 100 bpm.
  • Females with irregular menstrual cycles (oligomenorrhea) that ranges from 36-90 days, and females with the absence of a menstrual cycle (amenorrhea).
  • Taking birth control for the sole purpose of period cessation (eg., Mirena IUD)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Timothy D Mickleborough, PhD contact

812-855-0753

tmickleb@iu.edu

United States1 site, 1 recruiting
  • Multidisciplinary Engineering and Sciences Hall (MESH)

    Bloomington, Indiana, 47405

    Scott M Clarke, 812-856-3244, scotclar@iu.edu

    Zachary J Schalder, PhD, 812-855-6953, zschlade@iu.edu

    Recruiting

Other trials in United States

About this study

Official title: Optimizing Mind-Body Interactions in Respiratory Control During Operationally Relevant Environmental Stressors

Warfighters are frequently exposed to environments and life-support systems that increase breathing resistance and the work of breathing (WOB), such as aircraft on-board oxygen generation systems and underwater breathing apparatuses. Elevated WOB increases the perception of breathing difficulty (dyspnea) and has been associated with impaired cognitive performance, including slower reaction time and reduced accuracy during attention-demanding tasks. These effects are particularly concerning in operational settings that require rapid decision-making and precise motor responses.

Despite growing recognition of this issue, critical gaps remain regarding strategies to mitigate the perceptual and cognitive consequences of elevated inspiratory resistance, especially under realistic operational stressors. The objective of this study is to determine whether reducing mechanical WOB alters breathing perception and cognitive performance during inspiratory resistance. Participants will breathe either normal-density air or a low-density helium-oxygen gas mixture (heliox) to determine whether reducing mechanical WOB lowers perceived breathing effort and improves cognitive function.

Read the detailed description

Increases in the WOB intensify the sensory and emotional perceptions of dyspnea, at least partly due to heightened conscious awareness of breathing. Recent data indicate that elevated WOB, and likely breathing perception, can impair cognitive function. This impairment is likely caused by negative affective sensations resulting from the increased WOB, which distracts from central information processing during complex reaction-time tasks. Additionally, both reaction time and accuracy worsen when greater loads are placed on the inspiratory muscles. However, several key knowledge gaps remain that are pertinent to Warfighters that experience elevated inspiratory resistance. This study will investigate whether reducing the WOB during inspiratory resistance can lower breathing perception and restore cognitive function.

Heliox lowers the resistive WOB and muscle load because of its low density and viscosity, allowing for higher ventilation rates than room air by reducing turbulent flow in the airways. Therefore, breathing heliox, which will lower the WOB, under high inspiratory resistance will provide critical insights into whether reducing the WOB can improve cognitive function. It's hypothesized that using heliox will decrease the WOB, lower perceived breathing effort, and improve cognitive function compared to breathing normal density air with elevated inspiratory resistance.

Participants will complete two study visits: a screening/familiarization visit (Study Day 0) followed by one experimental visit (Study Day 1). Participants will be instructed to avoid caffeine, alcohol, stimulant medication, pain/anti-inflammatory medication, cannabis and cannabis related products, and vigorous exercise for at least 24 hours prior to experimental visits. On Study Day 0, participants will complete a short familiarization breathing task in which they will breathe for 10 minutes through an 8-10mm hole at the end of a customized device, generating a pre-determined inspiratory resistance of 6-9.5 centimeters of water per liter per second (cmH2O/L/s). During the breathing task, cerebral vascular, cardiovascular and autonomic activity responses will be measured. Every 5 minutes during the breathing test, participants will be asked to rate breathing intensity and unpleasantness, and perform an inspiratory capacity maneuver. Cognitive assessments will be administered every10 minutes. After the breathing task, participants will complete lung and respiratory muscle function tests.

Prior to Study Day 1 (the experimental visit), participants will be randomized to the order in which they are exposed to the interventional conditions (room air or heliox). Upon arrival, an esophageal balloon will be placed to measure the pressure around the heart and lungs. Participants will then complete two full-length breathing tasks, in which they inspire against a predetermined resistive load for 60 minutes, while breathing under the assigned conditions in the order of randomization. Biometric monitoring, cognitive tasks and participant ratings during the breathing tasks will be completed with the same frequency as Study Day 0. A 1-hour rest period will be observed between the breathing tasks.

Being tested
Heliox inspirate
Keywords
Inspiratory Resistance, Dyspnea Perception, Cognitive Performance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Heliox inspirateDrug

    This intervention corresponds to Arm 1 titled "room air and heliox inspirate". This corresponds with the first phase/period of this study.

Study groups in NCT07424014
Study groupRoleWhat they receive
Room Air, then Heliox InspirateActive comparatorParticipants will complete 2 full length breathing tasks, one under each condition. The order of condition exposure will be assigned via randomization.
Receives: Drug: Heliox inspirate
Heliox Inspirate, then Room AirActive comparatorParticipants will complete 2 full length breathing tasks, one under each condition. The order of condition exposure will be assigned via randomization.
Receives: Drug: Heliox inspirate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Stroop Color-Word Test Time Performance

    Time performance on the Stroop Color-Word Test (min:sec) will be measured every 10 minutes during each breathing task.

    Measured: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

  2. Change in Stroop Color-Word Test Error Performance

    The number of errors on the Stroop Color-Word Test will be measured will be measured every 10 minutes during each breathing task.

    Measured: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

  3. Change in Perception of Dyspnea Intensity

    Participants will rate perception of dyspnea (breathing) intensity on a visual analog scale (VAS) every 5 minutes during each breathing task. The participant will draw a vertical marker line on a horizontal line (100mm),indicating their breathing perception from "not noticeable" (0mm) to "maximal imaginable intensity" (100mm).

    Measured: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

  4. Change in Perception of Dyspnea Unpleasantness

    Participants will rate perception of dyspnea (breathing) unpleasantness on a visual analog scale (VAS) every 5 minutes during each breathing task. The participant will draw a vertical marker line on a horizontal line(100mm), indicating their breathing perception from "not unpleasant"(0mm) to "maximal imaginable unpleasantness" (100mm).

    Measured: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

Secondary outcomes (8)
  1. Change in Work of Breathing - Esophageal Pressure

    Heliox-induced reduction in WOB will be summarized by pre- and post-values of pressure (unit: cmH2O) via esophageal balloon pressures during the heliox condition.

    Measured: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

  2. Change in Work of Breathing - Mouth Pressure

    Heliox-induced reduction in WOB will be summarized by pre- and post-values of pressure (unit: cmH2O) via esophageal balloon pressures, mouth pressure, and dynamic lung volumes during the heliox condition.

    Measured: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

  3. Change in Work of Breathing - Dynamic Lung Volume

    Heliox-induced reduction in WOB will be summarized by pre- and post-values of pressure (unit: cmH2O) via dynamic lung volumes during the heliox condition.

    Measured: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

  4. Change in Cerebral Blood Velocity

    Bilateral transcranial Doppler Ultrasound will be used to continuously measure middle and posterior cerebral artery blood velocity during each breathing task. The ultrasound transducers will be placed on both sides of the head at the temporal windows and the positions will be fixed using a transducer holder.

    Measured: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

  5. Change in Cerebral Blood Oxygen Kinetics

    Oxyhemoglobin and deoxyhemoglobin (uptake/extraction, uM) will be measured continuously via near-infrared spectroscopy (NIRS) of the pre-frontal cortex during each breathing task.

    Measured: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

  6. Change in Heart Rate

    Heart Rate will be measured continuously during each breathing task by 3-lead electrocardiograph (ECG).

    Measured: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

  7. Change in Blood Pressure - Finger Photoplethysmography

    Blood pressure will be measured continuously during each breathing task via finger photoplethysmography.

    Measured: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

  8. Change in Blood Pressure - Brachial Artery

    Blood pressure will be measured every 10 minutes during each breathing task via a standard blood pressure cuff and auscultation of the brachial artery.

    Measured: Before and after each Day 1 breathing task (approximately 60 minutes in duration)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Feb 2026
  2. Study start3 Feb 2026
  3. Primary completion31 May 2027 (estimated)
  4. Study completion31 May 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07424014
Sponsor's protocol ID
28381 - Aim 1
Other IDs
FOAAFRLAFOSR20240007
Status last verified
Mar 2026
First submitted
18 Dec 2025
Last updated
12 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: The plan to share individual participant data (IPD) is still unknown. However, if other researchers request IPD, we will evaluate that request and determine to share IPD.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in