Amyotrophic Lateral Sclerosis, Primary Lateral Sclerosis, Progressive Muscular Atrophy
Conditions
Brief summary
This is a single-session, case-control study that incorporates digital tools for assessing speech and motor function in motor neuron disease. Patients with motor neuron disease (including amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), and progressive muscular atrophy (PMA)) and age-matched healthy controls will be enrolled. Subjects will complete a speech and handwriting assessment during the study visit on a tablet computer (BioSensics LLC, Newton, MA). We will explore whether these digital biomarkers are sensitive to functional disease severity as reported by the ALS Functional Rating Scale - Revised (ALFRS-R) \[1\]. We will also compare assessment data between the patient and control groups.
Detailed description
ALS is a progressive neuromuscular disease that causes weakness and inevitably affecting multiple motor processes within the body. To assess changes in functional mobility, clinicians and clinical investigators often rely on the ALS Functional Rating Scale - Revised (ALSFRS-R), a standardized 12-item questionnaire that has been in use for decades. Although thoroughly validated, this scale has received criticism for providing a coarse reflection of a patient's disease, scaling non-linearly within and across functional domains, and without the sensitivity to reflect day-to-day variability or small but meaningful changes. This study includes collection of digital speech and fine motor control assessment data at a single study visit. Features extracted from this data will be compared with standard clinical disease outcome measures and also the features derived from control participant data. We will use these comparisons to explore the use of these digital assessments in capturing the range of functional changes that occur in ALS and the related motor neuron diseases of PLS and PMA that are regularly treated in the ALS clinic.
Interventions
BEHAVIORALDigital Speech and Handwriting Assessment
Subjects may complete all or some of these tests, depending on functional ability. * Handwriting battery * Pattern tracing battery * Speech Assessment Battery
Sponsors
Milton S. Hershey Medical Center
BioSensics
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. \[Patient Group Only\] Diagnosis of definite, probable, probable laboratory-supported, or possible ALS by revised El Escorial research criteria \[Brooks2000\], primary lateral sclerosis (PLS), or progressive muscular atrophy (PMA). 2. \[Patient Group Only\] at least minimal speech or handwriting ability 1. ALSFRS-R speech score of 2 ("intelligible speech with repeating") or greater, OR 2. ALSFRS-R handwriting score of 2 ("not all words are legible") or greater. 3. \[Control Group Only\] Possess no neurological or orthopedic problems that affects their speech or handwriting AND age-matched to the existing patient cohort. 4. 18 years of age or older; 5. Fluent in written and spoken English.
Exclusion criteria
1. Currently or previously enrolled in STUDY00013892 (NCT05271435) 2. Neurological or orthopedic problems (independent of their inclusionary diagnosis for the patient group) that affects their speech or handwriting 3. Pregnant or nursing woman 4. Prisoner or institutionalized individuals 5. Have any clinically relevant medical history of other disease or diseases that, in the opinion of the research team, exclude the subject from participation (including severe cognitive dysfunction).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Speaking rate during a standardized passage | baseline | Speaking rate, in words per minute, will be determined from an audio recording of a standardized reading passage. |
| Residual on spiral tracing task | baseline | Handwriting tasks include tracing of a spiral. The average residual, or deviation from the target spiral (in pixels), will be determined from the handwriting file associated with the tracing task. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ALS Functional Rating Scale- Revised (ALSFRS-R) | baseline | The ALSFRS-R measures 12 aspects of physical function, ranging from one's ability to swallow and use utensils to climbing stairs and breathing. Each function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. |
| Forced vital capacity (FVC) | baseline | FVC is collected at clinical appointments by a respiratory therapist. FVC is the volume of air that is forcefully expelled into a spirometer. FVC is expressed as a percentage (%) of predicted volume against an age, height, and ethnicity matched standard. The best result of three trials is used. |
| Upper motor neuron function | baseline | Reflex testing is performed by the attending neurologist at clinical appointments. Bilateral biceps, triceps, and brachioradialis reflexes will be documented according to Modified Ashworth Scale grade 0 (no tone increase) to 4 (limb rigid). Total score for bilateral muscle groups ranges from 0 to 24. |
| Strength testing | baseline | Strength testing is performed by the attending neurologist at clinical appointments. Bilateral deltoids, biceps, triceps, wrist extension, and interossei strength will be documented according to Medical Research Council (MRC) grade 0 (no power) to 5 (normal power). Total score for bilateral muscle groups ranges from 0 to 50. |
Countries
United States
Outcome results
None listed