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

• ClinicalTrials.gov Identifier: NCT03645031
• Recruitment Status: Recruiting
• First Posted: August 24, 2018
• Last Update Posted: July 20, 2020
• Sponsor: University of Florida
• Information provided by (Responsible Party): University of Florida

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis (ALS); Neuromuscular Diseases	Other: Acute Intermittent Hypoxia; Other: Sham Acute Intermittent Hypoxia	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Participants will complete both the AIH and the sham AIH visits. The order of these visits will be randomized, but all subjects will complete both visits in the course of the study.
• Masking: Single (Participant)
• Masking Description: Participants will be blind to the order of the AIH/sham AIH visits, but this information will be provided to the participant after completion of last visit.
• Primary Purpose: Treatment
• Official Title: Acute Intermittent Hypoxia and Breathing in Neuromuscular Disease
• Actual Study Start Date: October 1, 2018
• Estimated Primary Completion Date: March 2021
• Estimated Study Completion Date: June 2021

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: Sham AIH

Outcome Measures

Primary Outcome Measures :

1. Maximal Respiratory Pressures [ Time Frame: 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.
2. 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 with <10% variability, and a minimum 15-second rest between measurements.

Secondary Outcome Measures :

1. Minute Ventilation [ Time Frame: 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.
2. Ventilatory Drive [ Time Frame: 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.
3. Surface electromyography (EMG) [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Barbara K Smith, PT, PhD; (352) 294-5315; bksmith@phhp.ufl.edu

Contact: Jessica Ehrbar, MS; (352) 273-6855; jehrbar@ufl.edu

Locations

United States, Florida

UF Clinical Research Center; Recruiting

Gainesville, Florida, United States, 32610

University of Florida; Recruiting

Gainesville, Florida, United States, 32611

Sponsors and Collaborators

University of Florida

Investigators

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

More Information

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT03645031
• Other Study ID Numbers: IRB201801131; OCR18018 ( Other Identifier: OnCore )
• First Posted: August 24, 2018
• Last Update Posted: July 20, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Florida:

acute intermittent hypoxia (AIH); respiratory motor function; hypoxia; normoxia; EMG (electromyography)

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Neuromuscular Diseases; Hypoxia; Neurodegenerative Diseases; Nervous System Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Signs and Symptoms, Respiratory