Acute Intermittent Hypoxia and Breathing in Neuromuscular Disease (AIH in ALS)

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.

Study Overview

• Status: Completed
• Conditions: Neuromuscular Diseases; Amyotrophic Lateral Sclerosis (ALS)
• Intervention / Treatment: Other: Acute Intermittent Hypoxia; Other: Sham Acute Intermittent Hypoxia

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Barbara K Smith, PT, PhD; Phone Number: (352) 294-5315; Email: bksmith@phhp.ufl.edu
• Study Contact Backup: Name: Juliette J Clavier, BS; Phone Number: (352) 273-6855; Email: Juliette.Clavier@phhp.ufl.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida
    • Gainesville, Florida, United States, 32610
      • UF Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALS Group; 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.	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.; Other Names: AIH; Other: 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.; Other Names: Sham AIH
Experimental: Healthy Control Group; 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.	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.; Other Names: AIH; Other: 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.; Other Names: Sham AIH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Barbara K Smith, PT, PhD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): June 2, 2023
• Study Completion (Actual): June 2, 2023

Study Registration Dates

• First Submitted: August 22, 2018
• First Submitted That Met QC Criteria: August 22, 2018
• First Posted (Actual): August 24, 2018

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: hypoxia; normoxia; acute intermittent hypoxia (AIH); respiratory motor function; EMG (electromyography)
• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Signs and Symptoms, Respiratory; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Hypoxia; Neuromuscular Diseases
• Other Study ID Numbers: IRB201801131; OCR18018 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No