An interventional study of Acute Intermittent Hypoxia and Sham Acute Intermittent Hypoxia in Amyotrophic Lateral Sclerosis (ALS) and Neuromuscular Diseases, sponsored by University of Florida. Completed at 2 sites in United States. Open to participants aged 21 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-05-15.
Sponsored by University of Florida · Not applicable, Interventional, and Treatment
This project seeks to investigate the effects of a single acute intermittent hypoxia (AIH) session on respiratory and non-respiratory motor function and EMG (electromyography) activity on patients with ALS (amyotrophic lateral sclerosis) and healthy controls.
Most ALS patients survive less than 5 years after diagnosis, and the main cause of death is respiratory failure. The investigators are interested in the therapeutic potential of acute intermittent hypoxia (AIH) for individuals with neuromuscular diseases, such as ALS. More than two decades of research indicates AIH elicits meaningful respiratory and non-respiratory motor recovery. Acute intermittent hypoxia (AIH) consists of alternating periods of breathing mildly hypoxic (lowered oxygen concentration) and normoxic (normal oxygen concentration) air.
The investigators propose to study mechanisms of respiratory plasticity associated with a single presentation of mild AIH. The fundamental hypothesis guiding this proposal is that even a single AIH trial improves respiratory (and non-respiratory) motor function in ALS patients procedure. Participants will then be asked to breathe air with reduced oxygen for short periods of time, for a duration of 45 minutes. The activity of your muscles and your heart function will be monitored throughout the procedure.
717 studies on the registry are indexed under Motor Neuron Disease; 137 are open to participants now.
This study's enrollment of 29 is below the median of 35 across 461 interventional studies indexed under Motor Neuron Disease.
Browse Motor Neuron Disease studies →University of Florida is the lead sponsor of 1,254 studies on the registry; 201 are open to participants now.
Of its 170 completed or terminated interventional studies of FDA-regulated products, 136 (80%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants will complete a single 45 minute session of acute intermittent hypoxia (AIH), as well as, the 45 minute sham AIH session, consisting of breathing air with normal oxygen levels. Breathing, muscle activity and heart activity will be monitored before, during and after both procedures.
Other: Acute Intermittent Hypoxia · Other: Sham Acute Intermittent Hypoxia
Participants will complete a single 45 minute session of acute intermittent hypoxia (AIH), as well as, the 45 minute sham AIH session, consisting of breathing air with normal oxygen levels. Breathing, muscle activity and heart activity will be monitored before, during and after both procedures.
Other: Acute Intermittent Hypoxia · Other: Sham Acute Intermittent Hypoxia
AIH entails continuous breathing as the level of oxygen in the air is decreased, then returned to normal. Participants will alternate between breathing normal air and breathing hypoxic air (air that has less oxygen). Participants will complete a single 45 minute session of acute intermittent hypoxia (AIH). Breathing, muscle activity and heart activity will be monitored before, during and after the procedure. The intervals will last 1 minute each.
Also known as: AIH
Participants will complete the sham acute intermittent hypoxia, consisting of a single 45 minute session of breathing air with normal oxygen levels. All aspects of this procedure will otherwise be the same as for the AIH procedure. Breathing, muscle activity and heart activity will be monitored before, during and after the procedure.
Also known as: Sham AIH
Percent Change in Maximal Inspiratory Pressure (MIP)
MIP is a maximal voluntary static contraction of the inspiratory muscles against a closed valve, measured at the mouth. The test will be repeated until 3 measurements are obtained within 10% variability and an average of the three trials is reported. The change in MIP will be the percent difference in pressure between the averaged baseline MIP and the averaged follow-up measure, which is tested 60 minutes after the gas intervention.
Time frame: 3 Hours
Percent Change in Maximal Voluntary Grip Force
Maximal static voluntary handgrip contractions will be evaluated in a seated position with the arm at the side and elbow flexed to 90 degrees. The test will be repeated until 3 measurements are obtained within 10% variability and then averaged. The change in grip will be the percent difference in force between the averaged baseline grip and the averaged follow-up grip measure, which is tested 60 minutes after the gas intervention.
Time frame: 3 Hours
Percent Change in Sniff Nasal Inspiratory Pressure
Maximal voluntary contractions of the inspiratory muscles measured with a pressure sensor placed in the nare. The test will be repeated until 3 measurements are obtained within 10% variability and then averaged. The change in sniff nasal inspiratory pressure will be the percent difference in pressure between the averaged baseline sniff nasal inspiratory pressure and the averaged follow-up measure, which is tested 60 minutes after the gas intervention.
Time frame: 3 Hours
Percent Change in Minute Ventilation
Minute ventilation is measured using a pneumotachograph connected to the face mask to record breath-by-breath volume and breathing rate, which is then multiplied to calculate minute ventilation. After achieving a stable tidal volume, 5 minutes of resting minute ventilation will be recorded and then averaged. The change in minute ventilation will be the percent difference in volume between the averaged baseline ventilation and the averaged follow-up ventilation, which is tested 60 minutes after the gas intervention.
Time frame: 3 Hours
Occlusion Pressure (P0.1)
P0.1 is measured with a pressure transducer connected to a face mask and represents the pressure generated against a transiently occluded airway in the first 0.1 sec of inspiration. The generated during this initial period of inspiration is resistant to learning or sensory bias and is considered a clinical estimate of inspiratory drive. Five measurements will be conducted and then averaged, with 5-15 un-occluded breaths between each P0.1 measurement. The averaged pressures at baseline and 60 minutes post-gas intervention will be reported and will be expressed in cm H2O.
Time frame: 3 Hours
Percentage Change in Respiratory EMG Vector Magnitude
EMG vector magnitude represents the composite surface EMG activity expressed from eight respiratory muscles (bilateral scalene, sternocleidomastoid, 2nd parasternal, and 8th external intercostal/diaphragm). The vector magnitude was calculated for each participant from the root mean square (RMS) values from each EMG channel, as the square root of the sum of the individual squared EMG channel amplitudes.
Time frame: 3 Hours
| Milestone | ALS Group - AIH Followed by Sham | Healthy Control Group - AIH Followed by Sham Hypoxia | ALS Group, Sham Followed by AIH | Healthy Control Group, Sham Followed by AIH |
|---|---|---|---|---|
| Started | 7 | 8 | 8 | 6 |
| Completed | 6 | 6 | 8 | 4 |
| Not completed | 1 | 2 | 0 | 2 |
MIP is a maximal voluntary static contraction of the inspiratory muscles against a closed valve, measured at the mouth. The test will be repeated until 3 measurements are obtained within 10% variability and an average of the three trials is reported. The change in MIP will be the percent difference in pressure between the averaged baseline MIP and the averaged follow-up measure, which is tested 60 minutes after the gas intervention.
| percentage change in MIP from baseline | ALS Group | Healthy Control Group |
|---|---|---|
| Sham Hypoxia | 0.3 ± 2.9 | -3.1 ± 2.3 |
| AIH | -4.8 ± 1.6 | -5.0 ± 3.2 |
Maximal static voluntary handgrip contractions will be evaluated in a seated position with the arm at the side and elbow flexed to 90 degrees. The test will be repeated until 3 measurements are obtained within 10% variability and then averaged. The change in grip will be the percent difference in force between the averaged baseline grip and the averaged follow-up grip measure, which is tested 60 minutes after the gas intervention.
| percent change in grip forcfrom baseline | ALS Group | Unaffected Control Group |
|---|---|---|
| AIH | -8.2 ± 0.26 | -11.2 ± 0.24 |
| SHAM | 14.5 ± 0.11 | 18.2 ± 0.07 |
Maximal voluntary contractions of the inspiratory muscles measured with a pressure sensor placed in the nare. The test will be repeated until 3 measurements are obtained within 10% variability and then averaged. The change in sniff nasal inspiratory pressure will be the percent difference in pressure between the averaged baseline sniff nasal inspiratory pressure and the averaged follow-up measure, which is tested 60 minutes after the gas intervention.
| Percent Change from Baseline | ALS Group | Healthy Control Group |
|---|---|---|
| Sham | 2.5 ± 4.1 | 7.4 ± 5.9 |
| AIH | 4.9 ± 5.0 | 5.8 ± 5.5 |
Minute ventilation is measured using a pneumotachograph connected to the face mask to record breath-by-breath volume and breathing rate, which is then multiplied to calculate minute ventilation. After achieving a stable tidal volume, 5 minutes of resting minute ventilation will be recorded and then averaged. The change in minute ventilation will be the percent difference in volume between the averaged baseline ventilation and the averaged follow-up ventilation, which is tested 60 minutes after the gas intervention.
| percentage change from baseline | ALS Group | Healthy Control Group |
|---|---|---|
| Sham hypoxia | 5.7 ± 7.3 | -5.6 ± 5.4 |
| AIH | 19.5 ± 6.0 | 2.6 ± 7.2 |
P0.1 is measured with a pressure transducer connected to a face mask and represents the pressure generated against a transiently occluded airway in the first 0.1 sec of inspiration. The generated during this initial period of inspiration is resistant to learning or sensory bias and is considered a clinical estimate of inspiratory drive. Five measurements will be conducted and then averaged, with 5-15 un-occluded breaths between each P0.1 measurement. The averaged pressures at baseline and 60 minutes post-gas intervention will be reported and will be expressed in cm H2O.
| cm H2O | ALS Group | Healthy Control Group | ALS Group - Sham Hypoxia | Control Group |
|---|---|---|---|---|
| Baseline | -0.80 ± 0.58 | -0.60 ± 0.41 | — | — |
| 60 minutes post-AIH | -0.83 ± 0.72 | -0.47 ± 0.53 | — | — |
EMG vector magnitude represents the composite surface EMG activity expressed from eight respiratory muscles (bilateral scalene, sternocleidomastoid, 2nd parasternal, and 8th external intercostal/diaphragm). The vector magnitude was calculated for each participant from the root mean square (RMS) values from each EMG channel, as the square root of the sum of the individual squared EMG channel amplitudes.
| percentage change from baseline | ALS Group | Healthy Control Group |
|---|---|---|
| Sham hypoxia | -24.5 ± 4.1 | 7.4 ± 13.1 |
| AIH | 179.8 ± 45.9 | 352.3 ± 99.4 |
Collected over Adverse events were collected from subject consent through 1 week following the last study visit. This timeframe is approximately 6 weeks.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| ALS- AIH Group | 0/14 (0%) | 0/14 (0%) | 2/14 (14.3%) |
| Healthy Control- AIH Group | 0/11 (0%) | 0/11 (0%) | 1/11 (9.1%) |
| ALS- SHAM GROUP | 0/14 (0%) | 0/14 (0%) | 4/14 (28.6%) |
| Healthy Control- SHAM Group | 0/11 (0%) | 0/11 (0%) | 0/11 (0%) |
| Event | ALS- AIH Group | Healthy Control- AIH Group | ALS- SHAM GROUP | Healthy Control- SHAM Group |
|---|---|---|---|---|
| Upper respiratory congestionRespiratory, thoracic and mediastinal disorders | 0/14 | 1/11 | 1/14 | 0/11 |
| Cough and sore throatRespiratory, thoracic and mediastinal disorders | 1/14 | 0/11 | 1/14 | 0/11 |
| Wrist sprainMusculoskeletal and connective tissue disorders | 0/14 | 0/11 | 1/14 | 0/11 |
| ShinglesSkin and subcutaneous tissue disorders | 0/14 | 0/11 | 1/14 | 0/11 |
| TachycardiaCardiac disorders | 1/14 | 0/11 | 0/14 | 0/11 |
Patients with an ALS diagnosis and age matched healthy controls.
| Age, Categorical(Participants) | ALS Group | Healthy Control Group | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 6 | 3 | 9 |
| >=65 years | 7 | 7 | 14 |
| Age, Continuous(years) | ALS Group | Healthy Control Group | Total |
|---|---|---|---|
| Mean | 65.3 (56 to 72) | 67.4 (60 to 75) | 66.2 (56 to 75) |
| Sex: Female, Male(Participants) | ALS Group | Healthy Control Group | Total |
|---|---|---|---|
| Female | 3 | 4 | 7 |
| Male | 10 | 6 | 16 |
| Ethnicity (NIH/OMB)(Participants) | ALS Group | Healthy Control Group | Total |
|---|---|---|---|
| Hispanic or Latino | 2 | 0 | 2 |
| Not Hispanic or Latino | 11 | 10 | 21 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | ALS Group | Healthy Control Group | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 2 | 2 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 13 | 8 | 21 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(Participants) | ALS Group | Healthy Control Group | Total |
|---|---|---|---|
| United States | 13 | 10 | 23 |
| Vital capacity (% predicted)(Percentage) | ALS Group | Healthy Control Group | Total |
|---|---|---|---|
| Mean | 83.3 (61 to 113) | 105.2 (86 to 132) | 92.8 (61 to 132) |
| Amyotrophic Lateral Sclerosis Functional Rating Scale- Revised (ALS-RFS-R)(units on a scale) | ALS Group | Healthy Control Group | Total |
|---|---|---|---|
| Mean | 38.8 (33 to 45) | — | 38.8 (33 to 45) |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No
This study is completed, as verified in May 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of Florida