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

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

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.

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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


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




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.



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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03645031


Contacts
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Contact: Barbara K Smith, PT, PhD (352) 294-5315 bksmith@phhp.ufl.edu
Contact: Jessica Ehrbar, MS (352) 273-6855 jehrbar@ufl.edu

Locations
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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
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Principal Investigator: Barbara K Smith, PT, PhD University of Florida
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Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT03645031    
Other Study ID Numbers: IRB201801131
OCR18018 ( Other Identifier: OnCore )
First Posted: August 24, 2018    Key Record Dates
Last Update Posted: July 20, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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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