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Completed

NCT Number: NCT03645031

Acute Intermittent Hypoxia and Breathing in Neuromuscular Disease

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.

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Key information

Conditions

Amyotrophic Lateral Sclerosis (ALS) Amyotrophic Lateral Sclerosis Central Nervous System Diseases Hypoxia Metabolic Diseases Motor Neuron Disease Nervous System Diseases Neurodegenerative Diseases Neuromuscular Diseases Nutritional and Metabolic Diseases Pathological Conditions, Signs and Symptoms Proteostasis Deficiencies Signs and Symptoms Signs and Symptoms, Respiratory Spinal Cord Diseases TDP-43 Proteinopathies

Age range

21 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

UF Clinical Research Center, Gainesville, Florida, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

Acute Intermittent Hypoxia

Other

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.

Other names: AIH

Sham Acute Intermittent Hypoxia

Other

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.

Other names: Sham AIH

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

Secondary outcomes

  1. Percent Change in Minute Ventilation

    Time frame: 3 Hours

    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.

  2. Occlusion Pressure (P0.1)

    Time frame: 3 Hours

    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.

  3. Percentage Change in Respiratory EMG Vector Magnitude

    Time frame: 3 Hours

    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.

Sponsors and collaborators

Lead sponsor

University of Florida

Other

Registry information

Acronym: AIH-ALS

Important dates

Study start
2018
Primary completion
2023
Study completion
2023
First posted
Aug 24, 2018
Registry last updated
May 15, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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