Acute Intermittent Hypoxia and Breathing in Neuromuscular Disease

Neuromuscular Diseases Clinical Trial

— AIH in ALS  

Official title:

Acute Intermittent Hypoxia and Breathing in Neuromuscular Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03645031
• Other study ID #: IRB201801131
• Secondary ID: OCR18018
• Status: Completed
• Phase: N/A
• Start date: October 1, 2018
• Est. completion date: June 2, 2023

Study information

• Verified date: June 2023
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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 information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: June 2, 2023
• Est. primary completion date: June 2, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Amyotrophic Lateral Sclerosis (ALS)
• Hypoxia
• Motor Neuron Disease
• Neuromuscular Diseases

Intervention

Other:
• 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.
• Sham Acute Intermittent Hypoxia
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.

Locations

Country	Name	City	State
United States	UF Clinical Research Center	Gainesville	Florida
United States	University of Florida	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal Respiratory Pressures	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.	3 Hours
Primary	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 with <10% variability, and a minimum 15-second rest between measurements.	3 Hours
Secondary	Minute Ventilation	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.	3 Hours
Secondary	Ventilatory Drive	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.	3 Hours
Secondary	Surface electromyography (EMG)	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.	3 Hours