Speech, Linguistic and Acoustic Markers in Parkinson's Disease
Conditions: Parkinson Disease, Cognitive Impairment, Mild, Speech
Sponsor: University of Massachusetts, Worcester

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ID: 
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   Speech, Linguistic and Acoustic Markers in 
Parkinson's Disease 
   NCT04273672
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1) 
Title 
Speech, language and acoustic markers in Parkinson disease (SLAM-PD) 
 
2) 
IRB Review History* 
NA, this is the initial application. 
 
3) 
Objectives* 
1) To develop markers of cognitive function in Parkinson’s disease (PD) 
that can be assessed through speech and language  
We hypothesize that speech and language tasks will yield biomarkers that 
can serve as proxies for performance on standard cognitive measures 
2) To assess the feasibility of implementing technology such as 
smartphone applications and tablet-based tasks to aid in the monitoring 
of vocal biomarkers in PD 
We hypothesize PD patients will be amenable and able to perform mobile 
app collection of vocal biomarker data. 
3) To evaluate the impact of motor, cognitive, and affective symptoms 
and therapy on vocal biomarkers. 
We hypothesize that vocal biomarkers of disease burden will fluctuate 
based on therapeutic response and will correlate to severity of motor, 
cognitive, and affective symptoms.  
 
4) 
Background* 
 
Speech impairment occurs in almost 90% of individuals with Parkinson disease (PD)1. 
PD patients have characteristic changes in speech, including changes in the coordination, 
changes in frequency and amplitude, changes in rhythm and rate, and changes in vocal 
quality, including breathiness, harshness, and hypernasality2. Changes in PD speech are 
thought to be caused by the neurodegenerative process of PD, specifically the impact on 
dopaminergic neurons in the substantia nigra and the subsequent dysfunction in the basal 
ganglia, a brain circuit involved in motor and cognitive control. While general speech 
impairment in PD has been characterized relative to healthy individuals, it is unknown if 
certain speech characteristics reflect particular motor or cognitive symptoms. 
Additionally, speech impairment may vary within an individual in response to 
medications and other therapies.  
 
Changes in speech may also be sensitive to subtle, early symptoms in PD such as 
cognitive dysfunction. While it is known that cognitive changes frequently occur early in 
the course of PD, these subtle deficits may be difficult to detect clinically.  For instance, 

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PD patients may report word finding difficulty (WFD) during spontaneous speech before 
objective cognitive deficits develop. Spontaneous speech may be a powerful tool to 
assess a range of cognitive functions because it requires multiple simultaneous cognitive 
processes (e.g. lexical retrieval, grammatical and syntactical structing, organization of 
narrative) occurring in real-time to attain fluency and accuracy.  
 
Previous work in this area has focused on the relationship between vocal biomarkers and 
motor symptoms. Authors have successfully predicted PD motor severity based on 
several vocal features3,4. An observational study has recently identified a link between 
clinician-rated speech symptoms and cognitive decline5. However, rating scales do not 
capture the data-rich acoustic and linguistic characteristics of speech. To our knowledge, 
there are no published reports using quantitative, objective speech parameters to monitor 
cognitive function in PD. In preliminary work, we have identified a potential relationship 
between WFD and pausing in speech that may depend on the location of the pause within 
the sentence structure6. We have also identified a cluster of acoustic and phoneme-related 
parameters that correlate significantly with global cognition independently of motor 
severity7. We therefore hypothesize that by combining quantitative speech and language 
assessment, we will be able to develop valid, sensitive tools to detect, monitor and predict 
cognitive changes in PD. Since PD symptoms vary both within and between days, and in 
response to medications, we will also use smartphone and tablet technology to obtain 
quick, remote and frequent speech data. By capitalizing on the ability to easily monitor 
speech remotely, we will develop assessment tools that can be implemented broadly.  
 
We propose to enroll PD patients with (n=50) and without (n=50) MCI and controls 
(n=50). We will compare speech acoustic and linguistic measures in tasks that evaluate 
speech production and comprehension. We will combine measures into models to 
discriminate by disease and cognitive status. Acoustic data will also be automated and 
assessed using machine-learning methods to enable future large scale data analysis. 
 
 
 
5) 
Inclusion and Exclusion Criteria* 
This study will include adult patients >18 years of age with no upper 
age limit with PD (diagnosed by a Movement Disorders specialist 
according to standard clinical diagnostic methods) and healthy controls 
(HC) who do not have PD or other neurological disorders. 
Patients and controls with dementia based on screening assessment 
(Montreal Cognitive Assessment, MoCA, score < 21) will be 
excluded.  
Patients without smartphone access will be excluded from the 
smartphone sub-study.   

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The following special populations will not be included: Adults unable 
to consent, individuals who are not yet adults (i.e., younger than 18 
years: infants, children, teenagers), pregnant women, and prisoners.  
Non-English speaking individuals will be excluded from this study 
since our linguistics outcomes of interest are based on norms and 
preliminary data from English speakers, and are specific to the 
grammatical and syntactic structure of the English language. 
People with visual impairment may be excluded because the speech 
and cognitive tasks are reaction timed measures and it would not be 
scientifically useful to include any subjects that require extra time for 
reading due to their vision or required use of braille. There are no 
standard norms available for these measures to correct for vision 
impairment, and the sample size will not be large enough for the study 
team to create those norms. However, reasonable accommodations will 
otherwise be made to include individuals with some degree of visual 
impairment. 
 
 
6) 
Study-Wide 
Number of 
Subjects* 
N/A 
 
7) 
Study-Wide 
Recruitment 
Methods* 
N/A This is not 
a multicenter 
study.  
 
8) 
Study Timelines* 
Planned enrollment duration- 24 months 
Planned duration of study for each participant-  main study: 1 screening 
session and 1 study visit less than 3 months apart; smartphone app sub-
study: 4 weeks following the study visit 
Table 5.1 Inclusion and Exclusion Criteria 
Group
Inclusion Criteria
Exclusion Criteria
PD
Diagnosis of PD 
(UK PD Brain Bank Criteria)8 
Any neurological disorder other than PD
Disease duration ≥ 2 years9
Deep brain stimulator placement
Severe, unstable psychiatric disorder
Unintelligible speech due to effects of PD 
PD and 
controls 
 
MCI or normal cognition
(MDS Task Force Level II 
criteria)10 
Diagnosis of dementia (DSM-5)
Age of PD onset >35 yrs or 
age>35 yrs (control) 
Non-English primary language speaker
Visual acuity or color vision impairment that 
would interfere with cognitive testing 
Other voice, speech or swallowing
disorders or history of surgery involving 
palate/nasopharynx/larynx/vocal cords 
Controls
Current or past history of any neurological 
disorder  

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Planned duration of the study- approximately 48 months. Approximately 
24 months to enroll and approximately 24 months for complex data 
analysis and development of analytical software and computerized 
algorithms.  
The goal is to begin actively enrolling into this study once IRB approval is 
received or November 2019 whichever comes first. Enrollment is 
estimated to be achieved by the fall of 2021. Data analysis is estimated 
to be completed by the fall of 2023.  
 
9) 
Study Endpoints* 
The primary outcomes will be 1) development of a model using speech 
acoustic markers to classify PD participants by cognitive status, 2) 
identification of linguistic markers (pausing, syntax) associated with 
cognitive status, and 3) identification of changes in speed and accuracy of 
syntax comprehension that correlate with cognitive status.  
10) Procedures Involved* 
Potential participants will undergo a preliminary screening session. 
Interested participants will be asked if they have Parkinson disease, their 
year of clinical diagnosis, and if they have deep brain stimulation for any 
indication. PD and control participant will be asked questions about 
neurological and psychiatric disorders and disorders or procedures that 
may have affected their voice (see screening questionnaire).  Both groups 
will be asked if they have a smartphone that is compatible with the Speech 
Vitals app (Aural Analytics, iOS running 12.4 or later, Andriod devices 
running 6.0 or later). 
If the potential participant meets all criteria, t, they will undergo a 
screening global cognitive assessment (Montreal Cognitive Assessment, 
MoCA). They will be excluded if MoCA <21. They will also be excluded 
if they have severe visual impairment such that they cannot comfortably 
read the text of the MoCA. , Screening sessions will occur in the offices of 
study personnel at UMass Memorial Medical Center or remotely via 
videoconference and will take approximately 30 minutes total. This video 
will not be stored. If time and space allow, this visit may be conducted on 
the same day as a participant’s regularly scheduled Neurology clinic visit, 
either before or after the physician visit. The participant’s name, phone 
number, appointment date/time, and yes/no if they were eligible will be 
recorded in a screening log. When enrollment is complete, the screening 
call log will be disposed of in a UMass Memorial Medical Center HIPAA-
compliant bin. Any collected data from participants who were ineligible or 
chose not to participate will thereby be destroyed.  

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All participants who remain eligible  will be educated about the study and 
undergo the informed consent procedure. Both the MoCA and HIPAA 
authorization are paper forms. If the participant is unable to come to 
UMass to complete these forms, they can be mailed or emailed to the 
participant prior to the initial visit and discussed in detail over 
videoconference to simulate the experience that would occur in the clinic 
setting. Any uncertainties regarding participant eligibility will be 
discussed directly with the study PI before any further study activities 
occur.  
The team plans to provide study documents such as the consent form and 
prompts for speech protocol in large font print for those with visual 
impairments. Similiarly, the language comprehension task on the laptop 
will be programmed with the largest font that is practical. 
Once a participant has signed the informed consent and HIPAA 
authorization, the following data will be collected by a member of the 
study team: 
 Basic demographic information: sex, age, years of 
education, duration of PD if applicable, list of medical 
conditions medication list (PD and controls, all 
medications) (<5 min) 
 Rating scale for symptom assessment and motor 
examination will be performed and rated by an experienced 
clinician on the study team (Movement Disorders Society 
Unified Parkinson Disease Rating Scale, MDS-UPDRS11) 
(<10 min) 
 Timed up and go (TUG)12, a timed mobility assessment of 
gait (<15 min) 
o For the TUG, participants will wear 4 wireless, 
Opal inertial sensors (APDM, Inc. sampling at 
128Hz) mounted on the sternum, waist, and on each 
foot, to quantify gait and joint kinematics.  
o The participants will perform the TUG once and the 
total time will be recorded. The participants will 
then perform the TUG while performing a dual-task 
of simultaneously listing words that begin with the 
letter “S” and the total time will be recorded.  
 Core cognitive/neuropsychological assessments (approx. 60 
min)- MoCA13, Trail-making test A & B, Symbol digit 
modalities test, Clock copy, Boston Naming Test (30 item 
odd), Animal naming, Letter-guided verbal fluency, 
Judgement of Line Orientation (15 item odd), Boston 
Diagnostic Aphasia Examination14 (BDAE; verb naming 

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and fluency, embedded sentences), digit span (WAIS-
R),Hopkins verbal learning test – R immediate, letter 
number sequencing, HVLT-R Delay and Recognition, brief 
visual memory test-R ), BVMT-R Delayed and 
Recognition. Other tests may be added if time permits- 
logical memory I (WMS-R, Anna Thompson story, logical 
memory II, Stroop (golden version), Shipley-2 vocab 
subtest)  Participants will be recorded while performing 
certain oral portions of the above measures.  
 Penn Daily Activities Questionnaire for Parkinson’s 
Disease17 (PDAQ) (5 min) 
 Geriatric depression scale18 (GDS) (1-2 min) 
 Parkinson’s Anxiety Scale19 (1-2 min) 
 Clinical Dementia Rating (CDR) worksheet: The 
participants will complete the subject section of the 
questionnaire during the study visit, and an informant or 
caregiver will also be contacted by phone after the study 
visit or in person if present at the study visit to complete the 
informant section of the questionnaire. During the visit, the 
CDR should only take 5 minutes with the participant. The 
CDR administered during the follow-up phone call to the 
informant or caregiver should take between 10 and 15 
minutes. 
 Speech and language production measures: participants will 
be recorded while performing a variety of standard speech 
and language tests (including but not limited to sustained 
phonation of vowel sounds, reading nonsense words, 
reading sentences and passages, description of a picture of 
a scene, sentences that include a Stroop color-word task)  
 After the study visit, please note that the study team may re-contact 
participants via phone if further color discrimination testing is 
deemed necessary based on subject results. The rationale for 
further color discrimination testing is based on prior research 
showing that Parkinson’s disease contributes to some degree of 
color discrimination deficit.  If participants agree to do the color 
discrimination testing, they will take a D15 Color Hue Test and a 
traditional Stroop Test via Zoom. Each assessment should take no 
more than 5 minutes to complete.  
 
 Participants will be asked to perform manual copying and drawing 
tasks on a Microsoft Surface tablet while speaking. The tablet will 

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record voice, facial expression, and kinematics of writing/drawing. 
(<15 min) 
 Respiratory function will be assessed by incentive 
spirometry measuring peak inspiratory volume (<5 min) 
 To assess language processing, subjects will perform a self-
paced reading task. On a computer screen, subjects will be 
presented with a word that is part of a sentence. They will 
read the word and then push a button to advance to the next 
word. Sentences will vary in syntactical complexity. 
Comprehension will be assessed by instructing the subject 
to select the picture correctly illustrating the sentence from 
multiple choices. We will optimize experimental set-up for 
PD patients (e.g. large, easy-to-push button).(20 min) If 
time allows, participants may also complete a guided 
sentence completion task in which they will be asked to 
construct a sentence to describe a series of pictures. (5 min) 
 
A sub-group of participants will be invited to participate in an extension study 
using a smartphone application called Speech Vitals (Aural Analytics). These 
participants will use the app on their personal smartphone once weekly for 4 
weeks (or 4 times total over 8 weeks if they have difficulty with weekly 
measurements). The app will prompt the user through about 10 minutes of 
speaking tasks. 
 A blood sample will be drawn from peripheral venous stick 
to send for genetic analysis for PD and dementia-related 
genes. 
Participants will be assigned to either the PD or HC groups depending on 
their clinical interview / exam.  
Estimated total study visit time is 3-4 hours. Participants will be asked 
frequently if they require a break. If a participant asks to stop the study 
protocol due to fatigue, they will be allowed to return another day to 
complete the protocol if they wish. Participants will be compensated for a 
single study visit, with a $20 gift card.  
All speech recordings will be performed using a head-mounted voice 
recorder.  
Due to the COVID-19 pandemic, we will allow participants to complete 
the screening visit and portions of the study visit remotely via password-
secured Zoom videoconference. These virtual participants must have a 
device with camera to be able to join a Zoom meeting. They must also 
have a smartphone to participate in using the Speech vitals app. It has 
become clinically acceptable to perform many components of 
neuropsychological evaluation via telehealth. Cognitive tests requiring 

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paper forms for the participant to write on will be mailed to participants, 
with each test enclosed in a separate enveloped marked “do not open until 
study visit” to avoid practice opportunities. The virtual study participants 
will only perform the picture description task from the speech protocol. 
This portion of the virtual visit alone will be recorded for subsequent 
transcription and analysis. Virtual participants will not perform the 
majority of the speech protocol, the language laptop task, the dual-tasking 
drawing/writing task, or the blood draw for genetic markers on the virutal 
visit day. They will be enrolled in the smartphone sub-study for 4-8 
weeks. They will be asked to come in person to UMMS within 6 months 
to complete the remainder of the study activities. They will not need to 
repeat cognitive testing done previously, but will need to repeat the speech 
recording of the picture description. They will receive compensation only 
at the in person visit. The virtual opportunity will be offered at time of 
study enrollment, and participants may choose a one-time in person study 
visit, or a virtual visit followed by in person study visit. The rationale is 
that not all participants are comfortable with in person contact and this 
situation remains variable and evolving. Our new structure will allow 
recruitment to proceed more flexibility, bearing in mind the concerns of 
our older patient population. If a participant completes the virtual visit but 
not the in person visit due to any reason, their data will be included but 
they will not be counted toward the overall enrollment targets and will not 
receive financial compensation. 
There will not be long-term follow-up data collected. The participant will 
be reminded at study completion that they may be contacted in the future 
for follow-up or related studies (as indicated in the consent form) unless 
they contact the study team to decline this option. The PI’s contact 
information will be provided at this time for this purpose. Documentation 
of those who decline will be kept by the PI to ensure these patients are not 
contacted.  
All relevant assessment tools and questionnaires are attached.  
We will be processing blood samples for later analysis at VA Puget Sound 
Healthcare System. This will include spinning the blood in a centrifuge 
and aliquoting plasma and buffy coat with a pipette. No analysis will be 
taking place at UMass, only the centrifuging and aliquoting. Aliquoted 
samples will be stored in a freezer in the Clinical Research Center. 
Aliquoting will take place under a ventilated hood. Waste will be disposed 
of in the proper biohazard containers. We will be working in the Clinical 
Research Center under IBC I-631-15. 
 
Smartphone and tablet procedures 
Speech Vitals smartphone application (Aural Analytics): Speech Vitals is 
HIPAA- and GDPR-compliant mobile application and system developed 

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by Aural Analytics to collect and analyze speech in clinical studies. It’s 
available for use on iOS and Android devices through the Apple Store and 
Google Play Store, respectively. The app is downloaded onto the 
participant’s personal phone. Participants sign in using a study-provided 
user ID and password. The ID and password don't contain any personal 
information. Techical support questions should be directed to the UMass 
study team, who will work with Aural Analytics to resolve the issue. A 
Microsoft Surface tablet will be configured with specialized software for 
the dual-task procedures. Participants will be asked to perform various 
speaking tasks while copying shapes and drawing. Voice, facial 
expression, and manual kinematics will be automatically recorded with 
time stamp. The UMass study team members will be trainied by MIT 
Lincoln Lab (MIT LL) collaborators in the proper and safe use of 
audio/video recording.  
 
 
 
11) Data and Specimen Banking* 
Blood/plasma samples will be taken and shared with VA Puget Sound 
Health Care System in the bank of Dr. Cyrus Zabetian. It will be plasma 
sent and analyzed for LRRK2, GBA and ApoE4 genes. All samples will 
be de-identified before being sent. They will be stored indefinitely. Blood 
will be stored in locked freezers on a locked floor in the lab at VA Pugent 
Sound. Only laboratory personnel on the protocol will have access to the 
samples via possession of a key. For future use of the specimen, Dr. 
Zabetian’s research group and local collaborators at the VA Puget Sound 
Health Care System and University of Washington will be granted access. 
Specimen may be provided to other collaborators but this will be 
discussed with Dr. Smith first. 
The lab will also share coded genotype and linked clinical data with the 
NIH Database of Genotype and Phenotype (dbGaP). All information 
shared will be de-identified. Information may also be shared with National 
Institute on Aging Genetics of Alzheimer's Disease Data Storage Site. 
 
Data will not be banked. See #26 Confidentiality 
 
12) Data Management* 
Data Analysis Plan: 

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Aim 1. Statistical analysis- To use speech acoustic markers to estimate cognitive 
status, we will employ two co-primary outcomes; cognitive diagnosis and MoCA. 
Gaussian staircase (GS) regression will be used to predict these outcomes. 
Individual models will be developed to distinguish PD from controls and 
determine cognitive status. For MoCA, 3-4 cut points will be determined 
empirically. ROC curves will be used to quantify detection of these groups for 
each outcome and performance will be summarized using the area under the 
curve (AUC) statistic. We will assess for interactions by sex and age  
 
Sample size/power- Our prior work used MoCA as the primary outcome with 35 
mostly cognitively intact subjects. Enrolling subjects with a wider range of 
cognitive function will increase power to detect more granular MoCA cut points. 
We estimate that 50 PD-MCI will be sufficient to classify by MCI status and 
estimate 3-4 MoCA cut points as a measure of severity and clinically meaningful 
change for future clinical trials.  
 
Aim 2. Statistical analysis- To use 
linguistic markers to detect PD-MCI, 
the primary outcome is the number of 
pauses before verbs/100 verbs and, 
as secondary outcomes, total within-
utterance pause duration, number of 
pauses before nouns/100 nouns, 
modified words per minute, and 
percentage well-formed sentences. 
The primary analysis of these 
outcomes will be a non-linear mixed model with the three-level predictor of group 
membership (control, PD-MCI, PD with normal cognition) as the parameter of 
interest in the model. Standard ANOVA will be used as the global test of 
differences followed by pairwise t-tests.  
 
 
Aim 3. Statistical analysis- To identify the syntax processing signature of PD-
MCI, the primary outcome will be the timed efficiency of syntax processing. The 
total response time to complete each self-paced sentence will be calculated. 
Response times will be segregated by correct vs. incorrect response to the 
comprehension question. Syntax processing efficiency score will be calculated by 
dividing the percentage of correct responses by processing time for object-
relative and subject-relative categories. We will create multilevel models and test 
for effect of group (PD-MCI, PD normal cognition, control), sentence type, and 
interaction. We will create linear regressions for individual subjects using the 
listening times for all words and calculate residuals for the critical word in 
objective-relative clauses. We will assess correlations between the averaged 
residuals and global cognition (MoCA) and other neuropsychological tests to 
determine the relationship between online processing and cognitive measures.  

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13) Provisions to Monitor the Data to Ensure the Safety of Subjects* 
This research does not involve more than minimal risk to subjects.  
There is a risk of research data being lost or exposed. We will take all 
reasonable measures to ensure this does not occur (see #15 and 26), 
including use of secure databases and data-sharing mechanisms with 
collaborators.  
There is also a risk of information being lost or exposed through Amazon 
cloud.  
The Geriatric Depression Scale will be examined at the time of the first 
encounter with the study subject, and if the subject screens positive for 
depression (>5 points), the patient will be advised to speak with their 
treating physician.  
A color blindness test will be performed before the Stroop task. If a 
participant fails and is not previously known to be color-blind, they 
will be referred to ophthalmology.  
14) Withdrawal of Subjects* 
The study investigators do not foresee any potential causes to withdraw 
subjects. It is not expected that a participant may become cognitively 
impaired within the study period, given that the natural course of PD is 
very slowly progressive with cognitive changes over years not months.  
15) Risks to Subjects* 
This research does not involve more than minimal risk to subjects. 
The risks are low, which would be time burden, possible frustration and 
there is a small risk that this study could increase stress.   
Breach of confidentiality: One of the risks of being in this study is that the 
subject’s personal information could be lost or exposed. This is very unlikely to 
happen, and we will do everything we can to make sure that the subject’s personal 
information is protected.   
 With blood draw comes the risk of slight pain due to the needle puncture. The 
point of blood draw may become black and blue but this is harmless. The arm 
drawn from may be sore. Infection, light-headedness and fainting are also possible 
but unlikely. 
 

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16) Potential Benefits to Subjects* 
We do not expect individual participants to benefit from participating in 
this studyThe knowledge gained from this research study may be of 
benefit to future PD patients.   
17) Vulnerable Populations* 
No children, pregnant women or prisoners will be enrolled. Minorities will 
be recruited/enrolled in the same manner as other study participants, but 
will be required to speak English. This is because the pilot version of the 
app will be available only in English. Based on the success of the pilot and 
resources available, the company hopes to expand the app to other 
languages. The study will not involve cognitively impaired adults. The 
cognitive ability of each candidate will be assessed using the Montreal 
Cognitive Assessment and persons with dementia will be excluded.        
18) Multi-Site Research* 
N/A 
19) Community-Based Participatory Research* 
N/A 
20) Sharing of Results with Subjects* 
Study participants may request to have any final published manuscript(s) 
shared with them.  
 
21) Setting 
Physical Setting: All study visits and assessments will take place in the 
Clinical Trials Unit or the offices of the research team at UMass 
Memorial University campus or via videoconferencing from 
participants’ homes to the offices of the research team at UMass. 
Recruiting will take place in the UMass Memorial Neurology clinic, 
and through recruitment flyers available at local rehabilitation centers, 
foundations and support groups. This trial is posted on 
clinicaltrials.gov and the Michael J Fox Foundation Trial Finder. If 
necessary, to increase recruitment, we will ask Movement disorders 
centers in Boston to post and circulate our flyer. To minimize selection 
bias, consecutive subjects who meet all eligibility criteria will be 
considered for enrollment.  
Intervention Setting: There is no intervention. In some participants 
smartphone-based assessments will be performed independently in the 
participant’s home environment.   

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22) Resources Available 
  This study will take about 75% effort to train, screen, enroll, complete   
   required tests and procedures, data enter, maintain equipment and  
 supplies, and work with the IRB. 
 
All study staff have current CITI certification and training on the security 
issues of maintaining confidential information. There will be training on all 
aspects of the trial.  
 
The roles of the study staff: 
 
PRINCIPAL INVESTIGATOR (PI) is responsible for all aspects of the study and 
will have overall responsibility to lead the site study team. The PI will oversee the 
accrual of appropriate subjects, the conduct of the study according to the protocol, 
and the collection of required data. The PI will consent subjects, take medical 
history, conduct physical exam and study assessments, maintain regulatory 
documents, evaluate eligibility, data completion, query resolution, adverse event 
monitoring/reporting, IRB communications, IRB continuing reviews, and all 
study evaluations.   
 
The PI has 10 years of experience in clinical research in PD. She has been PI on 
investigator-iniated, collaborative, and industy-sponsored clinical studies. She has 
also served on the University of Pennsylvania IRB.  
 
 
CO-INVESTIGATORS are other providers in the Movement Disorders Center at 
UMass who treat patients with PD. They will assist with recruitment, screening of 
potential subjects, and performing MDS-UPDRS.  
 
RESEARCH ASSISTANTS will assist with recruitment, screening of potential 
subjects, scheduling study visits, obtaining informed consent, taking medical 
history and medication lists, performing the cognitive, speech and language 
assessments, performing certain parts of the physical examination (including 
MDS-UPDRS rating if appropriate for level of experience deteremined by PI), 
and instructing participants on usage of the smartphone app. Research assistants 
also maintain regulatory documents and paper study documents, assist with 
creation and maintanence of a Redcap database, manage IRB communications, 
IRB continuing reviews, and all study evaluations.   
 
External Collaborators: The PI has informed collaborators from the following 
places that they do not fall under the jurisdiction of the UMMS IRB, and 
collaborators will obtain any necessary IRB approvals that they require. 
 
Aural Analytics: Responsible for providing the Speech Vitals smartphone 
application customized to our study protocol, assisting with IRB, task and 

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protocol support related to the app portion of the study. Responsible for 
overseeing the transfer, storage, data quality assurance, analysis of data collected 
from the app.  In working with the UMMS PI, they will have access to additional 
deidentified clinical and demographic data in order to provide subgroup analyses. 
Interaction with participants will be limited to technical support.  
 
MIT/Lincoln Labs: Responsible for collaborating with PI in analysis and 
interpretation of speech samples and data from the dual-task protocol using the 
Surface tablet. They will have access to speech samples with basic, deidentified 
clinical information such as disease status, motor and cognitive test scores. They 
will provide the technology for the tablet interface and will have access to the 
video, audio and kinematic data from study participants. MIT/LL employees will 
not have any interaction with study participants and will not have access to any 
PHI (including email address). There will be collaboration in abstract and 
manuscript preparation and future funding proposals based from the current work. 
 
Stepp Lab (Boston University): Responsible for mentoring the PI in acoustic 
processing, analysis and interpretation. Dr. Cara Stepp and her approved delegates 
may have access to speech samples and associated acoustic data, de-identified 
clinical information such as disease status, motor and cognitive test scores. There 
will be collaboration in abstract and manuscript preparation and future funding 
proposals based from the current work.  
 
VA Puget Sound Health Care System and Dr. Cyrus Zabetian: Responsible for 
receiving and processing the blood and plasma samples for genetic information. 
Dr. Zabetian also runs the bank which the samples will be stored in. Some 
information will be shared will the NIH Database of Genotype and Phenotype. 
 
Douglas Martini, PhD (UMass Amherst): Responsible for designing and 
implementing inertrial sensor portion of the protocol. Will provide and maintain 
the sensors and associated software required to obtain sensor data, analyze and 
interpret sensor data, and participate in manuscript preparation.  
 
Resources for participants: Participants are not anticipated to require any medical 
or psychological services related to their participation in the study. They will 
continue to access their regular medical and/or psychological care providers 
independently of the study.  
 
 
23) Prior Approvals 
Neurology Department Interim Chair, Brian Silver, MD 
 
24) Recruitment Methods 
 

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The recruitment goals are realistic and feasible based on the volume of PD 
patients seen at the UMass Neurology Movement Disorders Clinic. There 
are approximately 800 PD patients being actively followed in the clinic. 
Based on known prevalence of dementia in PD, we expect approximately 
75% of these patients will not have dementia and will be eligible for the 
study. Out of the approximately 600 eligible patients, we then expect to be 
able to enroll 20% (120 patients). In addition, we expect an additional 20-
30 patient referrals from outside sources and word-of-mouth within the 
local PD community. These sources combined should allow us to achieve 
our target of 100 patients within 12-24 months. We expect the recruitment 
of healthy controls through word-of-mouth and other methods to be more 
than adequate to meet our target goal of 50 age-matched healthy controls.  
 
Potential subjects will be identified and recruited by several methods: 
- 
Flyers placed in the UMass Neurology Clinic waiting room and clinic 
rooms (flyer attached) 
- 
Direct discussion and referral from the patient’s neurologist at UMass 
during routine clinic visits such that (a) the PI might recruit her own 
patients or (b) other providers might ask patients if they are willing to 
talk with a member of the study team. In the latter case, providers will 
either pass along a flyer and patients will contact the study team 
directly, or providers will contact the study team and ask them if they 
are available to talk with an interested patient. The providers will not 
share protected health information with the study team. 
The study team will advertise to the UMass community via UMMS 
newsletters and social media, outreach to local PD rehabilitation, and 
group exercisecenters (including but not limited to: Fairlawn 
Rehabilitation Center, Whittier Rehabilitation Center), DopaFit, support 
groups and charitable organizations (including but not limited to: Ashland 
Senior Center, Framingham Callahan Center, Westborough Good 
Shepherd Lutheran Center, Worcester St. Vincent Hospital,  and 
foundations such as the American Parkinson Disease Association about 
the study via discussion with the organizers of these groups and mailing of 
flyers. The Conquering Diseases Volunteer Registry will be informed 
through emails to this list. These sites have eagerly participated in 
referring PD patients to UMass trials in the past. They will direct 
interested individuals to the PI for additional information. The PI has 
informal working relationships with these sites as a leader in PD education 
and research outreach in the community. These sites will receive copies of 
the study flyer and will inform their PD populations about the study using 
the language on the flyer. Interested individuals will be directed to the PI’s 
contact information. No data will be shared between these sites and 
UMass.  

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- 
Once a potential subject is identified, they will be screened for 
eligibility by: 
- 
Either by phone or in person in the Neurology clinic, study personnel 
will confirm that the participant has a diagnosis of PD (or that they are 
a healthy controland otherwise meets inclusion/exclusion criteria. 
Participants who score <21 on MoCA will be excluded. ).  If they 
remain eligible and are interested in participating, they will be 
scheduled for an initial visit. Subjects will be compensated for their 
time and parking for the study visit (not the screening session), $20 per 
participant for the approximately 3 hour study visit in the form of a 
gift card.  
 
25) Local Number of Subjects 
Our goal is to screen 150 PD and 75 control subjects at UMass Memorial 
University campus and other local sites over a 12 month period. We 
anticipate no more than 25% screen failures. Approximately 100 patients 
and 50 healthy controls will therefore complete the research protocol 
which will be sufficient for the exploratory nature of this study.  
 
26) Confidentiality  
 
The information collected as data for this study includes: age, sex, years of 
education, medical history, medication list, PD disease duration, scores of 
motor and cognitive assessments, questionnaire responses, speech 
samples, linguistic and non-linguistic data from analysis of speech 
samples and syntax task, and facial expression and manual kinematics data 
from the dual-task procedure. 
 
Subject confidentiality will be strictly maintained by the use of study ID 
numbers.  
 
Speech data recorded during the study visit will be saved in wav file 
format, using only study ID in file name, and stored on password-
protected UMMS secured laptop with back-up on external hard drive kept 
in locked drawer in PI office.  Speech samples, facial expression, and 
manual kinematics data (labled with study ID only) may be shared through 
UMMS-approved secure data-sharing mechanisms with MIT-LL and 
Stepp lab collaborators designated by the PI.  
 
Inertial sensor data will be labeled only with study ID. Sensor data will be 
stored locally on the secure, password-protected UMMS laptop designated 
for study team use only and shared via UMMS-approved secure data-

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sharing mechanisms with Douglas Martini, PhD. This de-identified data 
will be stored on a password-protected secure UMass Amherst computer.  
Aural Analytics/smartphone app data: Speech recordings and metadata 
about the session are stored locally on the user's device until they are 
successfully uploaded to our HIPAA-compliant web servers, at which 
point they are deleted from the device. The data uploads anytime the app 
is open and device connected to internet. No demographic data that has 
meaning outside of the study context will be collected. IP addresses are 
not collected.  
The data is encrypted in transit and at rest on our servers. All data is 
hosted on AWS in the US behind secure API gateways and is access-
controlled so only trained and approved employees can access it. Meta-
data includes non-identifying information, such as time and data for the 
session and information about the participant’s device. Audio may be sent 
to a HIPAA-compliant transcription provider for transcription.  
The system calculated speech metrics from the audio files and these 
metrics are provided to the study PI at the end of the study via secure web 
portal.  
If a participant requires technical assistance or forgets their 
username/password for the app, they will contact the UMass study team 
who will act as the intermediary between the participant and Aural 
Analytics. Aural Analytics will not have direct contact with particiapnts in 
order to protect their privacy. 
 
MIT LL: Speech, facial expression, and kinematics data will be stored in a 
secure location at MIT LL under control of and accessible to Dr. Thomas 
Quatieri and Dr. James Williamson. Data will be stored in a secure, 
password protected limited access section of MIT LL LLAN networked 
computer system. The file server and workstations are all beind the MIT 
LL Firewall. At the conclusion of the study, a de-identified digital data set 
will be retaine for future modeling and algorithm development efforts, 
stored in a network folder at MIT LL for 10 years pas the study completed 
that is locked-down to an acess control list. Only members of the project 
team will have access to these project folders.  
 
The PI will collect the participants’ Speech Vitals username in order to 
create a key that links the Speech Vitals ID to the UMass study ID. This 
key will be stored securely in Redcap. Only the PI and designated study 
team members will have access to the REDCap key linking subject ID 
number with identifiers. Access to this key will be at the discretion of the 
PI and will not include Aural Analytics or their collaborations. 
 

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The PI will store her electronic records in a secure Redcap database which 
undergoes frequent back-up and security updates to protect integrity and 
confidentially of the data. This secure database will be password-
protected. The UMass study team will have access to the database 
(including identifying data) at the discretion of the PI. Data will be 
transferred out of Redcap only to an encrypted UMass network computer 
located in a locked office and files with de-identified clinical and 
demographic data will be shared with secure UMass file transfer site to 
collaborators (Aural Analytics, MIT LL, Dr. Cara Stepp). Speech files 
labeled with study ID only may be shared via UMass secure file transfer 
site with MIT LL and Dr. Stepp. All UMass study personnel will be able 
to enter data into the database.. The PI takes full responsibility for the 
secure storage, management and transmission of the data. 
 
All paper records will contain a study number rather than identifying information 
and will be stored in a locked cabinet in the PI’s locked office.  
The screening log, which necessarily contains identifiers, will be kept on a 
password-protected UMMS computer in the locked office of the PI.  
 
In accordance with UMass and federal policy, research records will be 
maintained for 3 years after completion of the study, and the HIPAA 
documents will be kept for 6 years after completion of the study. 
 
 
Videoconferencing will be completed through a secure, encrypted 
platform utilized routinely for telemedicine applications (doxy.me). In the 
case that doxy.me is not available or is not technically feasible for 
participants, alternatives will be used that contain equivalent privacy 
standards and are technically acceptable to the study investigators: VSee; 
Secure Video; TeleHealth365. 
 
UMass investigators will destroy the identifiers linking to data 5 years 
after the end of the study. This will involve destroying the REDCap 
project housing identifiers. We have no plans to destroy the deidentified 
data, as they would be used for continual research and development. At all 
times, we will limit the information being collected to only the pre-
specified data and questionnaires in the study protocol.  We will follow 
privacy obligations to study subjects under the Health Insurance 
Portability and Accountability Act (HIPAA). 
 
Only de-identified data will be used for dissemination of data outside the 
designated study team, and for publication of the data.  
 

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27) Provisions to Protect the Privacy Interests of Subjects (HIPAA) 
Participant assessment will take place in the Neurology clinic in a private room or 
remotely via videoconferencing to the participant’s home. If there is a need to 
leave a voicemail or message for a subject or potential subject, a message may be 
left that the call is in regards to a research study at UMass and a contact number 
for our study team will be provided, but no further details will be mentioned in the 
voicemail/message.  
All participants will sign a HIPAA form when enrolled into the study. Participation in 
the study will not affect their health or medical care.   
 
28) Compensation for Research-Related Injury 
This research involves only minimal risk to subjects. No funds have been 
set aside for compensation for research-related injury.  
29) Economic Burden to Subjects 
Participants will be responsible for transportation to study visits and for all 
fees related to smartphone data usage, according to their smartphone 
carrier agreement and plan.  
30) Consent Process 
The consent process will be implemented following “SOP: Informed Consent 
Process for Research (HRP-802 INVESTIGATOR GUIDANCE: Informed 
Consent. and HRP-803 INVESTIGATOR GUIDANCE: Documentation of 
Informed Consent).”     
 
In the UMass University Campus Neurology clinic, or via secure videoconference, 
the study personnel will educate potential study candidates on the purpose, 
procedures, possible risks and benefits, and subject responsibilities.  
 
Written informed consent will be obtained from each participant. It will be ensured 
that participants have ample time to review the consent form and that their 
questions or concerns are addressed. Study staff will highlight the fact that 
participation in the study is voluntary, and assure subjects and their families that the 
subject will receive the standard-of-care treatment of their neurologic condition 
regardless of their decision of whether or not to participate in the study, to protect 
the subjects from coercion or undue influence. Subjects with dementia will be 
excluded, thereby minimizing the possibility of invalid informed consent. The 
principal investigator or research assistant will be responsible for ensuring that a 
signed and dated informed consent is obtained from each subject prior to 
conducting any study-related activities. A copy of the consent form will be provided 
to each participant.    
 
31) Process to Document Consent in Writing 
 

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 Consent will be achieved referencing SOP “HRP-803 INVESTIGATOR 
 GUIDANCE:Documentation of Informed Consent ”.   
See #30 for consent process. 
Potential study participants will undergo a screening procedure prior to 
signing of consent. The study team will obtain verbal agreement for all 
procedures performed prior to signing of consent (including MoCA) 
before administration. 
Administration of the MoCA prior to written documentation of consent is 
not only a screening procedure for study eligibility, but will also determine 
whether a subject is capable of providing consent to participate. 
32) Drugs or Devices 
 
The app fits the following criteria for IDE exemption: 
 The device is a diagnostic device 
 The testing is noninvasive 
 The testing does not require an invasive sampling procedure that 
presents significant risk 
 The testing does not by design or intention introduce energy into a 
subject 
 The testing is not used as a diagnostic procedure without 
confirmation of the diagnosis by another, medically established 
diagnostic product or procedure 
 
The sponsor is responsible for labeling the device in accordance with 21 
CFR 809.10(c): “For Research Use Only. Not for use in diagnostic 
procedures.” 
 
 
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