Amyotrophic Lateral Sclerosis (ALS)AIH-ALSNCT03645031

Acute Intermittent Hypoxia and Breathing in Neuromuscular Disease

A study testing Acute Intermittent Hypoxia in people with Amyotrophic Lateral Sclerosis (ALS) and Neuromuscular Diseases, run by University of Florida at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 21 to 75 yearsHealthy volunteers can take part
Conditions the study is for: Amyotrophic Lateral Sclerosis (ALS), Neuromuscular Diseases
What is being tested?: Acute Intermittent Hypoxia
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 29 participants
Where: 2 sitesUnited States
Study dates: 1 Oct 2018to 2 Jun 2023
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 21 to 75 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

a healthy adult
clinical diagnosis of ALS
baseline FVC >60% predicted for age, sex and height.

Who cannot join

pregnant
diagnosed cardiovascular disease
a BMI >35 kg/m2
currently take selective serotonin reuptake inhibitors (SSRI)
history of seizures
history of hospitalization for sepsis

Show all 10Show fewer

respiratory infection or took antibiotic medications within the past 4 weeks
use external respiratory support during any waking hours
participate in a pharmaceutical trial to treat ALS
have any other medical condition the PI or medical director identify would make it unsuitable to participate.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

UF Clinical Research Center
Gainesville, Florida, 32610
University of Florida
Gainesville, Florida, 32611

Other trials in United States

About this study

Read the detailed description

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.

Conditions: Amyotrophic Lateral Sclerosis (ALS), Neuromuscular Diseases
Being tested: Acute Intermittent Hypoxia, Sham Acute Intermittent Hypoxia
Keywords: acute intermittent hypoxia (AIH), respiratory motor function, hypoxia, normoxia, EMG (electromyography)
Medical subject headings: Amyotrophic Lateral Sclerosis, Neuromuscular Diseases, Hypoxia

What participants receive

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

Acute Intermittent HypoxiaOther
Also called AIH
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.
Sham Acute Intermittent HypoxiaOther
Also called Sham 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.

Study groups in NCT03645031
Study group	Role	What they receive
ALS Group	Experimental	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. Receives: Other: Acute Intermittent Hypoxia; Other: Sham Acute Intermittent Hypoxia
Healthy Control Group	Experimental	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. Receives: Other: Acute Intermittent Hypoxia; Other: Sham Acute Intermittent Hypoxia

What is being measured

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

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.
Measured: 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.
Measured: 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.
Measured: 3 Hours

Secondary outcomes (3)

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.
Measured: 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.
Measured: 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.
Measured: 3 Hours

Timeline

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

1 Oct 20182 Jun 2023

First posted24 Aug 2018
Study start1 Oct 2018
Primary completion2 Jun 2023
Study completion2 Jun 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Amyotrophic Lateral Sclerosis (ALS)Studies of the same condition, open and under way.
More trials run by University of FloridaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: Participants will complete both the AIH and the sham AIH visits. The order of these visits will be randomized, but all subjects will complete both visits in the course of the study.
Masking: Single blind
Who is masked: Participant
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03645031
Sponsor's protocol ID: IRB201801131
Other IDs: OCR18018
Acronym: AIH-ALS
Status last verified: May 2025
First submitted: 22 Aug 2018
Last updated: 15 May 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Amyotrophic Lateral Sclerosis (ALS) trials

Study at a glance

From the registry record, last updated by the sponsor on 15 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Acute Intermittent Hypoxia and Breathing in Neuromuscular Disease
ClinicalTrials.gov ID: NCT03645031
Acronym / sponsor ID: AIH-ALS / IRB201801131
Conditions: Amyotrophic Lateral Sclerosis (ALS), Neuromuscular Diseases
Keywords: acute intermittent hypoxia (AIH), respiratory motor function, hypoxia, normoxia, EMG (electromyography)
Study type: Interventional
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: University of FloridaUniversity, hospital or other
Study start: 1 Oct 2018 (actual)
Primary completion: 2 Jun 2023 (actual)
Study completion: 2 Jun 2023 (actual)
First posted: 24 Aug 2018 (actual)
Results: Posted 15 May 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Single blind (participant)
Number of arms: 2
Model description: Participants will complete both the AIH and the sham AIH visits. The order of these visits will be randomized, but all subjects will complete both visits in the course of the study.

Arm	Type	Receives
ALS Group	Experimental	Other: Acute Intermittent Hypoxia, Other: Sham Acute Intermittent HypoxiaParticipants 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.
Healthy Control Group	Experimental	Other: Acute Intermittent Hypoxia, Other: Sham Acute Intermittent HypoxiaParticipants 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.

Who may qualify

Ages: 21 to 75 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

a healthy adult
clinical diagnosis of ALS
baseline FVC >60% predicted for age, sex and height.

Key exclusion criteria (10 listed)

pregnant
diagnosed cardiovascular disease
a BMI >35 kg/m2
currently take selective serotonin reuptake inhibitors (SSRI)
history of seizures

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Acute Intermittent HypoxiaAlso: AIHAIH 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.	Other	ALS Group, Healthy Control Group
Sham Acute Intermittent HypoxiaAlso: Sham AIHParticipants 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.	Other	ALS Group, Healthy Control Group

Primary outcome

Percent Change in Maximal Inspiratory Pressure (MIP)
Time frame: 3 Hours
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.
Percent Change in Maximal Voluntary Grip Force
Time frame: 3 Hours
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 Sniff Nasal Inspiratory Pressure
Time frame: 3 Hours
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.

3 secondary outcomes

Percent Change in Minute Ventilation
Time frame: 3 Hours
Occlusion Pressure (P0.1)
Time frame: 3 Hours
Percentage Change in Respiratory EMG Vector Magnitude
Time frame: 3 Hours

Results and safety

Results posted to the registry on 15 May 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ALS Group - AIH Followed by Sham	7	6
Healthy Control Group - AIH Followed by Sham Hypoxia	8	6
ALS Group, Sham Followed by AIH	8	8
Healthy Control Group, Sham Followed by AIH	6	4

Primary outcome: Percent Change in Maximal Inspiratory Pressure (MIP)

Time frame: 3 Hours. Mean (Standard Error). Unit: percentage change in MIP from baseline

Measure	ALS Group n = 13	Healthy Control Group n = 10
Sham Hypoxia	0.3 (2.9)	-3.1 (2.3)
AIH	-4.8 (1.6)	-5.0 (3.2)

Population analysed: Individuals with an ALS diagnosis and age matched healthy controls.

Primary outcome: Percent Change in Maximal Voluntary Grip Force

Time frame: 3 Hours. Mean (Standard Error). Unit: percent change in grip forcfrom baseline

Measure	ALS Group n = 13	Unaffected Control Group n = 10
AIH	-8.2 (0.26)	-11.2 (0.24)
SHAM	14.5 (0.11)	18.2 (0.07)

Population analysed: Individuals with an ALS diagnosis and age matched unaffected controls.

Primary outcome: Percent Change in Sniff Nasal Inspiratory Pressure

Time frame: 3 Hours. Mean (Standard Deviation). Unit: Percent Change from Baseline

Measure	ALS Group n = 13	Healthy Control Group n = 10
Sham	2.5 (4.1)	7.4 (5.9)
AIH	4.9 (5.0)	5.8 (5.5)

Population analysed: Individuals with an ALS diagnosis and age matched healthy controls.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected from subject consent through 1 week following the last study visit. This timeframe is approximately 6 weeks.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ALS- AIH Group	0 of 14 (0%)	2 of 14 (14.3%)	0 of 14
Healthy Control- AIH Group	0 of 11 (0%)	1 of 11 (9.1%)	0 of 11
ALS- SHAM GROUP	0 of 14 (0%)	4 of 14 (28.6%)	0 of 14
Healthy Control- SHAM Group	0 of 11 (0%)	0 of 11 (0%)	0 of 11

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Barbara K Smith, PT, PhD principal investigator

University of Florida

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Acute Intermittent Hypoxia in people with Amyotrophic Lateral Sclerosis (ALS) and Neuromuscular Diseases, run by University of Florida at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change in Maximal Inspiratory Pressure (MIP) (time frame: 3 Hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03645031.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2025.