Amyotrophic Lateral Sclerosis
Conditions
Keywords
Amyotrophic Lateral Sclerosis, Voice, Voice Quality, Total Lung Capacity
Brief summary
A disease called Amyotrophic lateral sclerosis (or ALS), which leads to difficulty swallowing, breathing, and movement, has been found to be higher for those serving in the military than in the general population. There are approximately 4,200 Veterans with ALS and roughly 1,000 new cases each year. When doctors attempt to determine the degree to which an ALS patient is suffering from the disease, they apply tests that are graded by experts. However, this approach to testing patients may not be very accurate. Researchers aim to use a system called DESIPHER to listen to ALS patients and find speech mistakes related to their condition. Researchers believe that, by detecting different types of errors, DESIPHER serves as a new kind of indicator of medical problems such as difficulty breathing or swallowing, without human grading. This may also lead to a better system for automatically understanding ALS patients' speech.
Detailed description
In 2008, Amyotrophic lateral sclerosis (ALS) or Lou Gehrig's Disease became a presumptively compensable (service connected) disease as the Institute of Medicine (IOM) Committee stated an association between the development of ALS and military service. According to the IOM report, military service increases life risk of ALS by 1.5 fold. There are approximately 4,200 Veterans with ALS and roughly 1,000 new cases each year. At the Tampa VA, since 2007, there has been a consistent rise in the number of Veterans diagnosed and treated with ALS. Most physiological assessments that are commonly used to determine the functional status of patients with ALS require trained clinical personnel to administer and interpret the results. The investigators propose to use automatic speech understanding and machine learning software (DESIPHER) to: identify speech pathologies and use them to predict other aspects of physiological degeneration associated with ALS (e.g., respiratory difficulty or inability to swallow), and ultimately improve speech recognition for those with speech impairments. The investigators expect this to improve the ability to appropriately identify and intervene when Veterans with ALS are at risk of serious adverse medical issues such as respiratory failure and aspiration. The investigators postulate that analyzing the overall divergence of (impaired) speech, from a normal baseline, will prove to be more robust and a better marker for involvement than others that have been proposed. Specific research questions to be addressed by this study are: (1) Is it possible to train a speech recognition system to adapt to increasingly more frequent language/speech errors of particular types, to produce an accurate textual transcript that would be readable by an ALS patient's caregiver or physician? (2) Are specific changes in physiological functioning: Forced Vital Capacity, tongue strength, speech velocity, weight (loss), aspiration risk, or psychological distress, reflected in different types of language/speech errors associated with ALS? By understanding how speech functioning correlates with the degree to which other biophysical functioning has degraded, it is possible to apply a new, non-invasive measure for assessing the functionality of an ALS patient. In addition, the features associated with speech degradation it is possible to adapt existing speech recognition software to a patient's speech as it evolves over time, so that the quality of life for patients may be improved through conversation with a computer. Respiratory failure is the main cause of morbidity and mortality in ALS patients. The investigators expect that the method of analyzing speech will present an excellent biomarker for respiratory function, as there is an expected increase in pauses during speech due to the necessity of increased frequency of respirations, a decrease in loudness, and decreased overall velocity of speech. A second major cause of death is aspiration. As the articular muscles decline, the investigators expect to note a decrease in the clarity of speech. Speech involvement often precedes swallowing involvement in ALS; thus, the investigators expect that increasing speech divergence will indicate potential aspiration risk.
Interventions
None listed
Sponsors
Study design
Eligibility
Inclusion criteria
* Veterans will be diagnosed with ALS * Native speakers of U.S. English * Will have bulbar involvement identified during initial ALS inpatient evaluation * Forced vital capacity (FVC) of greater than 50% of the expected value for age * An Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) Score of 40 or greater
Exclusion criteria
* A diagnosis of dementia * FVC less than 50% * Inability to speak * Or inability to follow directions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percent of Expected Lung Force Vital Capacity | Baseline, and every 3 months up to 24 months | Forced Vital Capacity (FVC) measures the ability of the lung to move air. The change in FVC was calculated from the initial time point to either the end of study (24 months) or to final visit due to either death or loss to followup. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Tongue Strength | Baseline, 3 Month intervals up to 24 months, calculated from the initial time point to either the end of study (24 months) or to final visit due to either death or loss to followup | A physiological measurement of tongue muscle strength, in multiple directions. A force measured with Iowa Oral Performance Instrument (IOPI) |
| Change in Speech - as Measured by Speech Divergence | Baseline, 3 Month intervals up to 24 months, calculated from the initial time point to either the end of study (24 months) or to final visit due to either death or loss to followup | A measure looking at changes in vocal characteristics away from standard language. Speech Divergence is a novel calculated measure based on identifying changes to 13 characteristics of speech. The score can range from 0-13. Zero would represent normal speech, while 13 would be distorted speech along all parameters. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the amyotrophic lateral sclerosis (ALS) Clinic at the James A. Haley Hospital from January 2016 to November 2017
Participants by arm
| Arm | Count |
|---|---|
| Veterans With ALS This Cohort Study will admit all eligible, interested Veterans diagnosed with ALS who meet the inclusion criteria. Veterans were at least 18 years old, and were diagnosed with ALS, and followed at the James A Haley VA Hospital | 15 |
| Healthy Controls Healthy Controls were recruited to complete a one time vocal recording of the TIMIT and Ba repetition voice recordings. | 19 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 |
Baseline characteristics
| Characteristic | Veterans With ALS | Healthy Controls | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 5 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 14 Participants | 22 Participants |
| Age, Continuous | 63.4 years STANDARD_DEVIATION 10.8 | 53.3 years STANDARD_DEVIATION 11.2 | 57.8 years STANDARD_DEVIATION 11.6 |
| ALS Functional Ratings Scale-Revised | 32.5 units Standardized Outcome Measu STANDARD_DEVIATION 7.4 | — | 32.5 units Standardized Outcome Measu STANDARD_DEVIATION 7.4 |
| Lip Strength | 15.5 kPa STANDARD_DEVIATION 9 | — | 15.5 kPa STANDARD_DEVIATION 9 |
| Percent of Predicted Forced Vital Capacity (FVC) | 69.1 Expected % Max FVC STANDARD_DEVIATION 21.9 | — | 69.1 Expected % Max FVC STANDARD_DEVIATION 21.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 16 Participants | 29 Participants |
| Sex: Female, Male Female | 1 Participants | 12 Participants | 13 Participants |
| Sex: Female, Male Male | 14 Participants | 7 Participants | 21 Participants |
| Speech Intelligence Test | 98.6 Percent words Intellegible STANDARD_DEVIATION 4.5 | — | 98.6 Percent words Intellegible STANDARD_DEVIATION 4.5 |
| Tongue Strength | 31.6 KPa STANDARD_DEVIATION 17.2 | — | 31.6 KPa STANDARD_DEVIATION 17.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 15 | 0 / 19 |
| other Total, other adverse events | 0 / 15 | 0 / 19 |
| serious Total, serious adverse events | 4 / 15 | 0 / 19 |
Outcome results
Change in Percent of Expected Lung Force Vital Capacity
Forced Vital Capacity (FVC) measures the ability of the lung to move air. The change in FVC was calculated from the initial time point to either the end of study (24 months) or to final visit due to either death or loss to followup.
Time frame: Baseline, and every 3 months up to 24 months
Population: Data for this measure were not collected for healthy controls.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Veterans With ALS | Change in Percent of Expected Lung Force Vital Capacity | -1.25 % Expected Forced Vital Capacity | Standard Deviation 7.05 |
Change in Speech - as Measured by Speech Divergence
A measure looking at changes in vocal characteristics away from standard language. Speech Divergence is a novel calculated measure based on identifying changes to 13 characteristics of speech. The score can range from 0-13. Zero would represent normal speech, while 13 would be distorted speech along all parameters.
Time frame: Baseline, 3 Month intervals up to 24 months, calculated from the initial time point to either the end of study (24 months) or to final visit due to either death or loss to followup
Population: Speech Divergence is a novel calculated measure for this study based on change in vocal characteristics of 13 characteristics. Speech Divergence was not collected for the Healthy Controls.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Veterans With ALS | Change in Speech - as Measured by Speech Divergence | 1.88 score on a scale | Standard Deviation 1.4 |
Change in Tongue Strength
A physiological measurement of tongue muscle strength, in multiple directions. A force measured with Iowa Oral Performance Instrument (IOPI)
Time frame: Baseline, 3 Month intervals up to 24 months, calculated from the initial time point to either the end of study (24 months) or to final visit due to either death or loss to followup
Population: Data for this measurement was only collected on the Veterans with ALS Arm. Data for this measure were not collected for healthy controls.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Veterans With ALS | Change in Tongue Strength | -.625 kPa | Standard Deviation 5.45 |