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| ID | Type | Description | Link |
|---|---|---|---|
| OCR18018 | Other Identifier | OnCore |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ALS Group | Experimental | 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 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Acute Intermittent Hypoxia | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in Maximal Inspiratory Pressure (MIP) | MIP is a maximal voluntary static contraction of the inspiratory muscles against a closed valve, measured at the mouth. The test will be repeated until 3 measurements are obtained within 10% variability and an average of the three trials is reported. The change in MIP will be the percent difference in pressure between the averaged baseline MIP and the averaged follow-up measure, which is tested 60 minutes after the gas intervention. | 3 Hours |
| Percent Change in 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 within 10% variability and then averaged. The change in grip will be the percent difference in force between the averaged baseline grip and the averaged follow-up grip measure, which is tested 60 minutes after the gas intervention. | 3 Hours |
| Percent Change in Sniff Nasal Inspiratory Pressure | Maximal voluntary contractions of the inspiratory muscles measured with a pressure sensor placed in the nare. The test will be repeated until 3 measurements are obtained within 10% variability and then averaged. The change in sniff nasal inspiratory pressure will be the percent difference in pressure between the averaged baseline sniff nasal inspiratory pressure and the averaged follow-up measure, which is tested 60 minutes after the gas intervention. | 3 Hours |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in Minute Ventilation | Minute ventilation is measured using a pneumotachograph connected to the face mask to record breath-by-breath volume and breathing rate, which is then multiplied to calculate minute ventilation. After achieving a stable tidal volume, 5 minutes of resting minute ventilation will be recorded and then averaged. The change in minute ventilation will be the percent difference in volume between the averaged baseline ventilation and the averaged follow-up ventilation, which is tested 60 minutes after the gas intervention. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Barbara K Smith, PT, PhD | University of Florida | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UF Clinical Research Center | Gainesville | Florida | 32610 | United States | ||
| University of Florida |
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| ID | Title | Description |
|---|---|---|
| FG000 | ALS Group - AIH Followed by Sham | 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 two weeks later. Breathing, muscle activity and heart activity will be monitored before, during and after both procedures. 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. |
| FG001 | Healthy Control Group - AIH Followed by Sham 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 two weeks later. Breathing, muscle activity and heart activity will be monitored before, during and after both procedures. 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. |
| FG002 | ALS Group, Sham Followed by AIH | Participants will complete a single 45 minute session of sham intermittent hypoxia consisting of breathing air with normal oxygen levels, as well as a single 45 minute session of acute intermittent hypoxia (AIH) two weeks later. Breathing, muscle activity and heart activity will be monitored before, during and after both procedures. |
| FG003 | Healthy Control Group, Sham Followed by AIH | Participants will complete a single 45 minute session of sham intermittent hypoxia consisting of breathing air with normal oxygen levels, as well as a single 45 minute session of acute intermittent hypoxia (AIH) two weeks later. Breathing, muscle activity and heart activity will be monitored before, during and after both procedures. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Patients with an ALS diagnosis and age matched healthy controls.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change in Maximal Inspiratory Pressure (MIP) | MIP is a maximal voluntary static contraction of the inspiratory muscles against a closed valve, measured at the mouth. The test will be repeated until 3 measurements are obtained within 10% variability and an average of the three trials is reported. The change in MIP will be the percent difference in pressure between the averaged baseline MIP and the averaged follow-up measure, which is tested 60 minutes after the gas intervention. | Individuals with an ALS diagnosis and age matched healthy controls. | Posted | Mean | Standard Error | percentage change in MIP from baseline | 3 Hours |
|
Adverse events were collected from subject consent through 1 week following the last study visit. This timeframe is approximately 6 weeks.
Adverse event definitions were consistent with clinicaltrials.gov definitions. Participants were asked at the beginning and end of every study visit to report any signs, symptoms, or occurrence that has occurred since their last encounter. Additionally, a final assessment was conducted by phone, approximately one week after the last study visit.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ALS- AIH 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. 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough and sore throat | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Barbara K. Smith | University of Florida | 352-294-5315 | bksmith@ufl.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 20, 2020 | Mar 28, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| D009468 | Neuromuscular Diseases |
| D000860 | Hypoxia |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
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| ID | Term |
|---|---|
| D007317 | Insemination, Artificial, Homologous |
| ID | Term |
|---|---|
| D007315 | Insemination, Artificial |
| D027724 | Reproductive Techniques, Assisted |
| D012099 | Reproductive Techniques |
| D013812 | Therapeutics |
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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.
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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.
|
|
| Sham Acute Intermittent Hypoxia | Other | 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. |
|
|
| 3 Hours |
| Occlusion Pressure (P0.1) | P0.1 is measured with a pressure transducer connected to a face mask and represents the pressure generated against a transiently occluded airway in the first 0.1 sec of inspiration. The generated during this initial period of inspiration is resistant to learning or sensory bias and is considered a clinical estimate of inspiratory drive. Five measurements will be conducted and then averaged, with 5-15 un-occluded breaths between each P0.1 measurement. The averaged pressures at baseline and 60 minutes post-gas intervention will be reported and will be expressed in cm H2O. | 3 Hours |
| Percentage Change in Respiratory EMG Vector Magnitude | EMG vector magnitude represents the composite surface EMG activity expressed from eight respiratory muscles (bilateral scalene, sternocleidomastoid, 2nd parasternal, and 8th external intercostal/diaphragm). The vector magnitude was calculated for each participant from the root mean square (RMS) values from each EMG channel, as the square root of the sum of the individual squared EMG channel amplitudes. | 3 Hours |
| Gainesville |
| Florida |
| 32611 |
| United States |
| BG001 | 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. 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Vital capacity (% predicted) | Mean | Full Range | Percentage |
|
| Amyotrophic Lateral Sclerosis Functional Rating Scale- Revised (ALS-RFS-R) | The ALS-FRS-R is a scale that reflects the functional impact of ALS. The score consists of 12 subsections each rated on scale from 0-4. The subsections include speech, salivation, swallowing, handwriting, feeding, dressing/hygiene, walking, climbing stairs, dyspnea, orthopnea, and respiratory insufficiency. The total score was reported and is the sum of the 12 subsections (0-48 points) where higher scores represent more preserved function. | The healthy controls do not have an ALS-FRS score. | Mean | Full Range | units on a scale |
|
| OG001 | 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. 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. |
|
|
| Primary | Percent Change in 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 within 10% variability and then averaged. The change in grip will be the percent difference in force between the averaged baseline grip and the averaged follow-up grip measure, which is tested 60 minutes after the gas intervention. | Individuals with an ALS diagnosis and age matched unaffected controls. | Posted | Mean | Standard Error | percent change in grip forcfrom baseline | 3 Hours |
|
|
|
| Primary | Percent Change in Sniff Nasal Inspiratory Pressure | Maximal voluntary contractions of the inspiratory muscles measured with a pressure sensor placed in the nare. The test will be repeated until 3 measurements are obtained within 10% variability and then averaged. The change in sniff nasal inspiratory pressure will be the percent difference in pressure between the averaged baseline sniff nasal inspiratory pressure and the averaged follow-up measure, which is tested 60 minutes after the gas intervention. | Individuals with an ALS diagnosis and age matched healthy controls. | Posted | Mean | Standard Deviation | Percent Change from Baseline | 3 Hours |
|
|
|
| Secondary | Percent Change in Minute Ventilation | Minute ventilation is measured using a pneumotachograph connected to the face mask to record breath-by-breath volume and breathing rate, which is then multiplied to calculate minute ventilation. After achieving a stable tidal volume, 5 minutes of resting minute ventilation will be recorded and then averaged. The change in minute ventilation will be the percent difference in volume between the averaged baseline ventilation and the averaged follow-up ventilation, which is tested 60 minutes after the gas intervention. | Individuals with an ALS diagnosis and age matched controls. | Posted | Mean | Standard Error | percentage change from baseline | 3 Hours |
|
|
|
| Secondary | Occlusion Pressure (P0.1) | P0.1 is measured with a pressure transducer connected to a face mask and represents the pressure generated against a transiently occluded airway in the first 0.1 sec of inspiration. The generated during this initial period of inspiration is resistant to learning or sensory bias and is considered a clinical estimate of inspiratory drive. Five measurements will be conducted and then averaged, with 5-15 un-occluded breaths between each P0.1 measurement. The averaged pressures at baseline and 60 minutes post-gas intervention will be reported and will be expressed in cm H2O. | Individuals with an ALS diagnosis and age matched healthy controls who completed a single exposure to acute intermittent hypoxia. P0.1 during sham hypoxia presentations were not collected due to an oversight by study staff and cannot be reported. | Posted | Mean | Standard Deviation | cm H2O | 3 Hours |
|
|
|
| Secondary | Percentage Change in Respiratory EMG Vector Magnitude | EMG vector magnitude represents the composite surface EMG activity expressed from eight respiratory muscles (bilateral scalene, sternocleidomastoid, 2nd parasternal, and 8th external intercostal/diaphragm). The vector magnitude was calculated for each participant from the root mean square (RMS) values from each EMG channel, as the square root of the sum of the individual squared EMG channel amplitudes. | Individuals with an ALS diagnosis and age matched controls. | Posted | Mean | Standard Error | percentage change from baseline | 3 Hours |
|
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| 2 |
| 14 |
| EG001 | Healthy Control- AIH 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. 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. | 0 | 11 | 0 | 11 | 1 | 11 |
| EG002 | ALS- SHAM 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. 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. | 0 | 14 | 0 | 14 | 4 | 14 |
| EG003 | Healthy Control- SHAM 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. 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. | 0 | 11 | 0 | 11 | 0 | 11 |
| Upper respiratory congestion | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Wrist sprain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Shingles | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Tachycardia | Cardiac disorders | Non-systematic Assessment |
|
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| D019636 | Neurodegenerative Diseases |
| D057177 | TDP-43 Proteinopathies |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008919 | Investigative Techniques |
| D007314 | Insemination |
| D012098 | Reproduction |
| D055703 | Reproductive Physiological Phenomena |
| D012101 | Reproductive and Urinary Physiological Phenomena |
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|