The Role of Heliox in Respiratory Control

NCT07424014 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: 28381 - Aim 1FOAAFRLAFOSR20240007
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Work of Breathing

Keywords

Inspiratory Resistance; Dyspnea Perception; Cognitive Performance

Outcome Measures

Primary Outcomes (4)

• 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.

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

• 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.

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

• 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).

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

• 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).

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

Secondary Outcomes (8)

• Change in Work of Breathing - Esophageal Pressure

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

• Change in Work of Breathing - Mouth Pressure

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

• Change in Work of Breathing - Dynamic Lung Volume

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

• Change in Cerebral Blood Velocity

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

• Change in Cerebral Blood Oxygen Kinetics

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

Study Arms (2)

Room Air, then Heliox Inspirate

ACTIVE COMPARATOR

Participants will complete 2 full length breathing tasks, one under each condition. The order of condition exposure will be assigned via randomization.

Drug: Heliox inspirate

Heliox Inspirate, then Room Air

ACTIVE COMPARATOR

Participants will complete 2 full length breathing tasks, one under each condition. The order of condition exposure will be assigned via randomization.

Drug: Heliox inspirate

Interventions

Heliox inspirate DRUG

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

Heliox Inspirate, then Room Air; Room Air, then Heliox Inspirate

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Indiana University: lead
• United States Department of Defense: collaborator

Study Sites (1)

Multidisciplinary Engineering and Sciences Hall (MESH)

Bloomington, Indiana, 47405, United States

RECRUITING

Central Study Contacts

Timothy D Mickleborough, PhD

CONTACT

812-855-0753; tmickleb@iu.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 18, 2025
• First Posted: February 20, 2026
• Study Start: February 3, 2026
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)