Speech Analysis in ALS Patients

• ClinicalTrials.gov Identifier: NCT03868345
• Recruitment Status: Recruiting
• Last Update Posted: March 11, 2019
• Sponsor: Barrow Neurological Institute
• Collaborator: Arizona State University
• Information provided by (Responsible Party): Jeremy Shefner, Barrow Neurological Institute

Study Description

Brief Summary:

The purpose of this study is to find out if changes in speech can signal changes in the ability to think or remember. ALS patients with and without cognitive dysfunction will be followed for one year. Every three months, patients will undergo a series of cognitive and basic clinical outcomes tests. In addition, participants will take home a study-provided tablet on which they will complete weekly speech recording activities.

Condition or disease
ALS; Amyotrophic Lateral Sclerosis; Lou Gehrig Disease

Detailed Description:

Cognitive dysfunction is increasingly recognized as a core feature of amyotrophic lateral sclerosis (ALS). With appropriate testing, up to 50% of ALS patients will show evidence of frontotemporal dysfunction. Approximately 15% of patients meet formal criteria for frontotemporal dementia (FTD). Certain genetic forms of ALS (e.g., mutations in C9orf72) have even higher incidences of FTD. The presence of cognitive abnormalities is an adverse risk factor for survival, and its presence influences the ability of patients to cooperate in clinical trials. However, screening for frontotemporal abnormalities is frequently not performed in ALS clinics, and tools for diagnosing cognitive dysfunction are either time consuming or insensitive. Additionally, the frequently co-existing dysarthria complicates the assessment and may mask more subtle cognitive deficits. Once identified, ways of following progressive decline are also lacking. In an ongoing study, it has been shown that a sophisticated suite of speech and language analytics, developed by two of the investigators, can identify abnormalities in cognitively normal ALS patients without speech symptoms, and predict important functional changes outside of the speech domain. In this study, investigators will evaluate both speech and language in 50 patients with ALS both with and without symptoms of cognitive decline. This evaluation will be paired with two cognitive screening tools frequently used in ALS clinics, the ALS Cognitive Behavioral Screen (ALS-CBS) and the Montreal Cognitive Assessment (MoCA). The investigators will evaluate the extent to which speech and language deficits precede abnormalities as measured by the above tools and determine whether cognitive change can be accurately followed over 12 months using speech and language measures. It is hypothesized that speech and language measures will accurately and sensitively predict cognitive changes. If so, such measures may be very useful in future studies of potential therapeutic agents for ALS-FTD and other dementias.

Study Design

• Study Type: Observational
• Estimated Enrollment: 50 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Speech Analysis in ALS Patients With and Without Cognitive Abnormalities: Evaluation of Sensitivity and Disease Progression
• Actual Study Start Date: February 18, 2019
• Estimated Primary Completion Date: August 31, 2019
• Estimated Study Completion Date: December 31, 2019

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Change in ability on Speech and Language Battery [ Time Frame: Weekly recordings for one year ]
   Speech recordings made at home via a tablet using the " SpeechAssess" app.

Secondary Outcome Measures :

1. Change in Montreal Cognitive Assessment [ Time Frame: Administered every three months for a year ]
   Cognitive screening tool
2. Change in ALS Cognitive Behavioral Screen [ Time Frame: Administered every three months for a year ]
   Cognitive screening tool
3. Change in Vital Capacity [ Time Frame: Administered every three months for a year ]
   Measure of breathing function
4. Change in Negative Inspiratory Force [ Time Frame: Administered every three months for a year ]
   Measure of nasal inhale capabilities
5. Change in "ALS Functional Rating Scale- Revised" [ Time Frame: Administered every three months for a year ]
   Questionnaire regarding daily functioning. Scale is measured from 0 to 48 points, with 48 being normal function and 0 indicating no functional abilities.

Biospecimen Retention:   Samples With DNA

Blood serum and blood plasma to be collected at three timepoints and retained in a biorepository.

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients with ALS, diagnosed as definite, probable, or possible ALS according to the modified El Escorial Criteria.

Criteria

Inclusion Criteria:

1. male or female, age 21 or older,
2. diagnosed with definite, probable, or possible ALS according to the modified El Escorial Criteria,
3. a score of 2 or greater on the speech question of the ALSFRS-R (i.e. speech is intelligible with occasional repetition),
4. continuous internet access at home,
5. willingness and medical ability to comply with scheduled visits and study procedures,
6. ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations,
7. geographic accessibility to study site,
8. for the 25 participants in Group 1, NO noted symptoms of frontotemporal cognitive dysfunction, and
9. for the 25 participants in Group 2, MUST have cognitive symptoms as noted either by themselves or a caregiver.

Exclusion Criteria:

1. unwilling or unable to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the participant's ability to comply with the protocol, and
2. any other reasons that, in the opinion of the PI, cause the candidate to be deemed unsuitable for entry into the study.

Contacts and Locations

Contacts

Contact: Kerisa Shelton, PhD; 602-406-6598; kerisa.shelton@dignityhealth.org

Locations

United States, Arizona

Barrow Neurological Institute; Recruiting

Phoenix, Arizona, United States, 85013

Contact: Jessie Duncan Jessie.Duncan@DignityHealth.org

Principal Investigator: Jeremy Shefner, MD

Principal Investigator: Shafeeq Ladha, MD

Sponsors and Collaborators

Barrow Neurological Institute

Arizona State University

More Information

• Responsible Party: Jeremy Shefner, Senior Vice President and Chair of Neurology, Barrow Neurological Institute
• ClinicalTrials.gov Identifier: NCT03868345
• Other Study ID Numbers: BNI-ALS-003
• First Posted: March 11, 2019
• Last Update Posted: March 11, 2019
• Last Verified: March 2019

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 Jeremy Shefner, Barrow Neurological Institute:

ALS; Cognitive dysfunction; Speech

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases