Acute Intermittent Hypoxia and Breathing in Neuromuscular Disease

Not Applicable

Completed

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

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

Inclusion Criteria

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.

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
Maximal Respiratory Pressures	3 Hours	Maximal voluntary static contractions of the inspiratory or expiratory muscles against a closed valve, measured at the mouth. Sniff nasal inspiratory pressure measures inspiratory force generation at the nose.The test will be repeated until 3 measurements are obtained within 10% variability; a minimum 20-second rest will be provided between hypoxic episodes.
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 with \<10% variability, and a minimum 15-second rest between measurements.

Secondary Outcome Measures

Name	Time	Method
Minute Ventilation	3 Hours	A pneumotachograph and pressure transducer connected to the face mask will record breath-by-breath flow, volume, mouth pressure, and breathing rate. After achieving a stable tidal volume, 5 minutes of tidal breathing will be recorded.
Ventilatory Drive	3 Hours	Respiratory drive will be estimated with pressure generation against a transiently occluded airway in the first 0.1 sec of inspiration. Five measurements will be conducted, with 5-15 un-occluded breaths between each P0.1 measurement. This validated test is resistant to learning or sensory bias and reflects unaltered neuromuscular effort.
Surface electromyography (EMG)	3 Hours	Surface EMGs of the respiratory muscles (up to six muscles, bilaterally: scalene, sternocleidomastoid, 2nd parasternal, 5th external intercostal, 8th external intercostal, and diaphragm) will be recorded during the test session. The root mean square (RMS) of each muscle will be averaged.

Locations (2): UF Clinical Research Center
🇺🇸
Gainesville, Florida, United States
University of Florida
🇺🇸
Gainesville, Florida, United States