Acute Intermittent Hypoxia and Breathing in Neuromuscular Disease

Not Applicable

Completed

Conditions: Amyotrophic Lateral Sclerosis (ALS)
Neuromuscular Diseases

Interventions: Other: Acute Intermittent Hypoxia
Other: Sham Acute Intermittent Hypoxia

Registration Number: NCT03645031

Lead Sponsor: University of Florida

Brief 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 29

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Healthy Control Group	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.
ALS Group	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.
Healthy Control Group	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.
ALS Group	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.

Primary Outcome Measures

Name	Time	Method
Percent Change in Maximal Inspiratory Pressure (MIP)	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	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	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 Outcome Measures

Name	Time	Method
Percent Change in Minute Ventilation	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.
Occlusion Pressure (P0.1)	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.
Percentage Change in Respiratory EMG Vector Magnitude	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.