Addressing Socioeconomic Disparities in Post-stroke Upper-extremity Disability Through the Development of an Accessible, New Tool
Phase: EARLY_PHASE1
Conditions: Stroke
Sponsor: Arizona State University

Title: New Tool to Enhance Post-stroke Upper Extremity Disability 
Study Protocol, Statistical Analysis Plan, and Informed Consent form 
ID Number: NCT05277389 
Document Date: 06/07/2024 
 
 

Study Protocol & Statistical Analysis Plan 
We will conduct a stratified, parallel-group, double-blind, randomized controlled trial of remotely 
delivered START treatment to individuals with severe-to-moderate stroke (with recruitment focused on 
individuals with low SES). Subjects and assessors will be blinded to the condition making the experiment 
double blind. Specifically, subjects will be told that we are exploring a new therapy that using different 
sounds to improve therapy. Parallel group design will ensure that subjects in the Control group are 
unaware that their “sounds” are softer than the START group. Trainers may become aware that a loud 
sound is present thus unique Assessor will evaluate clinical performance before and after training. 
Assessor will be a certified and practicing occupational therapist.   
Fifty-eight subjects will undergo baseline testing in the laboratory to establish their upper extremity 
impairment, spasticity, and function as well as their self-reported health-related quality of life. Next, 
subjects will participate in high-repetition training, 2 hr/day for 3 consecutive days focusing on 
functional object manipulation (details below). Subjects will either receive training with START or 
without (Control). Subjects will be re-tested immediately following training as well as one-month post to 
assess retention. Activity trackers will be deployed before (baseline), during, and after training. Aim 1 
will evaluate the ability of START to enhance therapy outcomes by assessing the % change clinical 
assessment of function, spasticity, impairment, and self-reported quality of life, functional 
independence, and arm usage. Aim 2 will focus on the capacity of these changes to 1) be retained and 2) 
impact subject’s self-reported quality of life. NOTE: While we are planning in-person baseline, end, and 
retention testing, in response to covid, we have established remote clinical screening (see Potential 
Challenges and Solutions).  
Study population and screening: A diverse set of individuals 
with stroke-induced upper-extremity paresis will be 
recruited consistent with the 2010 census results (Non-
Hispanic white: 69%, Hispanic: 12.5%, African American: 
12.3%, Asian: 3.6%, and American Indian: 0.9%). We will 
include equal numbers of males/females to further examine 
possible sex differences in treatment effects. As this 
proposal is geared at reducing post-stroke disparity in 
individuals with low SES, we put an emphasis on recruiting 
in this population (see Retention and Recruitment).  
Recruitment will proceed through 1) our multi-site 
collaborative registry of stroke survivors, 2) Barrow 
Neurological Institute’s NeuroRehabilitiation Clinics, and 3) 
Banner Medical University Hospital. The PI has used these 
sources for recruitment of stroke participants for the 
preliminary data for this project and for K99/R00HD073240. 
Based on our recruitment history, we expect to screen ~80 potential participants each year, 50 of whom 
we expect will fit all of our criteria and participate, with ~15% attrition.  
After being recruited, subjects will be first interviewed to determine their eligibility (Table 1). If they 
meet the criteria, they will come to the lab to complete baseline testing.  
Baseline Testing: Baseline testing will include biometrics, stroke injury information, clinical assessment 
of impairment, spasticity, and function, and patient health-related quality of life (see below). To confirm 
the stroke injury, recent and/or admittance MRIs, as well as radiology and neurology reports, will be 
used to confirm date, location, and type of stroke (e.g. ischemic, hemorrhagic). Biometric data (e.g., 
height, weight, demographics). Hearing tests will be administered (see inclusion criteria); however, it is 
Table 1: Recruitment Criteria 
Inclusion Criteria 
1) 
>18 years old 
2) 
Capacity to provide informed consent 
3) 
Cerebral stroke at least 6 months prior to 
testing 
4) 
Presence of severe-to-moderate upper 
extremity impairment (UEFM < 42/66)  
5) 
Corrected pure tone threshold (octave 
frequencies 250- 4000 Hz) norms for their 
age and gender27,28 NOTE: Audiometry 
data will be collected for all participants by 
lab personnel trained by an audiologist in a 
sound-attenuated booth. We expect that 
~30% of participants will use hearing aids; 
we will not exclude these individuals but 
rather include hearing aid use as a 
covariate in analyses. 
Exclusion Criteria 
6) 
Severe concurrent medical problems (e.g. 
uncontrolled cardiorespiratory impairment) 
7) 
Acute/painful condition/injury of upper 

notable that the START effect has been observed in individuals with hearing loss14,18. We will closely 
monitor and if needed include hearing capacity in statistical models.   
To assess impairment, function, and spasticity stroke participants will complete standard clinical 
assessments.  
(1) Impairment: The Upper-Extremity Fugl-Meyer (FMA-UE) will used to quantitatively evaluate 
impairment. The FMA-UE is one of the most commonly utilized measure of impairment both 
in clinical and research settings. It has excellent interrater and retest reliability. Severe-to-
moderate impairment will be defined as <42/66.  
(2) Function: The Action Research Arm Test (ARAT) will be used to quantify upper extremity 
function, coordination, and dexterity during tasks relevant to activities of daily living. Nearly 
all tasks have excellent internal consistency in addition to excellent test/retest and interrater 
reliability.  
(3) Spasticity: Due to high variability in test/retest and inter/intra-rater reliability, two tests will be 
administered to assess spasticity of the shoulder (ab/adduction) elbow (flex/extension), wrist 
(flex/extension), thumb (flex/extension), and hand (all digits – extension): Modified Ashworth 
(MA) and Modified Tardieu Scale (MTS). While MA is the more commonly administered test, 
it suffers from moderate/weak interrater reliability. The MTS, which is similar to the Ashworth 
but makes use of goniometers, has excellent test/retest reliability as well as interrater 
reliability. The modified Tardieu also includes Passive Range of Motion (PROM) which can 
be assessed independently.  
To assess patient’s health-related quality of life, we will administer the following generic preference-
based measures (GPMs).  
(1) The Stroke Impact Scale (SIS) is a self-report scale of disability and health-related quality of 
life. We will use the subdomains of hand function, ADL/IADL, and mobility. These domains 
have excellent test/retest reliability and excellent (hand function, mobility) or adequate 
(ADL/IADL) inter/interrater reliability. All tested domains also have excellent internal 
consistency.  
(2) Modified Rankin (MRS) is a patient reported outcome that categorizes functional 
independence with reference to pre-stroke activities. It has excellent test/retest and 
inter/intra-rater reliability.  
(3) Motor Activity Log (MAL) is a semi-structured interview of patient reported arm function. It 
has excellent test/retest reliability and internal consistency.  
Training protocol: During the baseline assessment, subjects will be given a training kit (Fig 2). The 
training kit includes: a phone (Pixel 2 - Google, Mountain View, CA; OS: Android 10, Chipset: Qualcomm 
MSM8998 Snapdragon 835) and headphones (JLab studio - JLab Audio, Carlsbad, CA; Drivers: 40mm 
neodymium; Frequency: 20Hz-20kHz) with a microphone which acts as a backup for audio recordings. 
The phone comes with a preloaded, custom-built, app developed using android studio with Java for 
functionality and Extensible Markup Language for the user interface. It can deliver randomly applied 
sounds per the specifications below and display recorded files and playback using a media player. The 
app is controlled remotely by the Trainer/Experimenter using AnyDesk App for Android (AnyDesk 
Software GmbH, Germany); thus, the phone app is controlled remotely by the experimenter. Subjects or 
caretakers are only responsible for charging the phone and do not have to perform any other actions to 
manipulate the phone. Further, this ensures that subjects cannot be exposed to loud, startling sounds 
unless explicitly delivered by the trainer.   
Subjects will receive 3 consecutive days of remote, telehealth sessions via secure video service. Upper 
extremity therapy for individuals with severe impairment focuses on tasks of functional significance e.g., 
self-feeding. For consistency across subjects and to allow statistical comparison, we have chosen 3 tasks 

related to self-feeding: hand extension, object lifting, and arm extension. For the hand extension task, 
subjects will be seated in front of an unopened, full, soda can. They will be asked to open their hand to 
grab the soda can. For object lifting, subjects will be asked to lift the soda can to their mouth. If they 
cannot grasp the can voluntarily or if it is too heavy, they will be assisted or given a small, light block or 
no object if necessary. Empty soda cans are often crushed by high hand spasticity in individuals with 
severe stroke; thus, a rigid object (e.g., block is used). For the arm extension task, a soda can will be 
placed at 80% arm’s length away from the subject’s body. Subjects will be asked to attempt to reach the 
soda can and touch it with their hand (grasp if able).   
Practice of these tasks will be modified to be amenable to the START protocol. Specifically, subjects will 
practice attempting each task following two non-startling (80dB SPL) acoustic cues. The first acoustic cue 
will indicate “get ready.” The second acoustic stimulus will indicate “move”. During START training, the 
“move” cue will be randomly replaced with a startling, acoustic stimulus of ~120dB over 0.04s. To 
reduce anticipation, which is required for a consistent START response, the startling stimulus will be 
applied during only 33% of trials. This protocol has been well established for generating the highest 
percentage of startles24. Each of the 5 training days, subjects will practice each task 45 times with 15 
trials accompanied by the startling, acoustic stimulus. The Control group subjects will practice each task 
the same amount of times (45) but none of the trials will include the startling, stimulus.  
End- and Retention- Testing: The same measures (except biometrics) evaluated during Baseline 
assessment (FMA-UE, ARAT, MA, MTS, SIS, MRS, MAL) will be collected on the final day of training as 
well as one-month post training. Finally, a questionnaire about START will be administered asking about 
ease of use, comfort, adverse side effects (none have ever been reported).  
Analysis for Aim 1: To establish that START can increase functional paretic limb usage, we will perform 
a randomized controlled trial assessing the impact of START on therapy outcomes. 
We hypothesize that training with START will increase paretic arm function (ARAT), self-reported arm 
function (MAL), and functional independence (mRS) compared to training without START. To assess this, 
we will evaluate effects of the treatment (START vs control) on a group of random subjects from a 
parallel group of stroke patients. The hypothesis expects a positive impact over multiple days of 
evaluation with respect to the baseline. We do not expect the data to conform to Gaussian norms. 
Therefore, we will utilize a generalized linear mixed model to identify differences between groups in this 
longitudinal data set. The treatment (START vs. control) and the day of testing (pre, post) will be setup 
as the fixed factors. Subjects will be treated as a random factor, nested within treatment. Tukey post-
hoc tests will be employed with a p-value <0.05 will be used to indicate significance. Analysis will be 
conducted using R’s lme4 package25.  
Analysis for Aim 2: To establish that START generates retainable changes that impact quality of life, 
we will re-assess upper-extremity function and self-reported quality of life (SIS, MRS). 
We hypothesize that A) START gains will be retained more than Control and B) retention will be 
associated with higher quality of life measures (e.g., SIS) one-month post-START training. For A, the 
same analysis as proposed above will be conducted except the day of testing will compare post-training 
to one-month post as the fixed factors. To complete the analysis for B, we will utilize a regression 
analysis between the change in the functional score and the change in the quality of life for each 
subject. The choice between a linear and a logistic regression will be determined by the data 
themselves. Analysis will be conducted in R, using the base R functionality. 
 
 

Consent Form: Bioscience  
Title of research study: The use of startle-evoked movement to evaluate reach and grasp (Hybrid Study)  
Investigator: Claire Honeycutt, Ph.D  
Why am I being invited to take part in a research study?  
You are being asked to be a subject in a research study about movement planning and learning. 
Our objective is to understand how planning and learning is interrupted by neurological disease and 
injury.  You have been asked to participate in the research because you had a stroke so we can 
understand how  an impaired individual performs these tasks.   
Why is this research being done?  
In order to learn a new task, one must develop a cohesive movement plan. We do not 
understand the  time course of this planning process as well as how complex and segmented tasks are 
planned. Our  long-term goal is to develop training programs for individuals with neurological disease 
and injury  
How long will the research last?  
The research study is conducted in a span of five days split into two parts: 1) Test sessions and 2)  
Training sessions.  Additionally, there will be a one month follow up test session. 
Each test session will take 3-4 hours and will occur no more than two times in a week. During 
these  test sessions, the effectiveness of the training is explored by evaluating your ability to reach and 
grasp  objects. Also, you will be asked to partake in an assessment to determine the severity of your  
impairment. Additionally, there will be a single test session of 3-4 hours one-month after your  
participation. In total, there will be 3 test sessions.  
Each training session will take 1-2 hours, where you will be asked to practice the movements and  
tasks, that was used for evaluating during the test sessions. These sessions will occur no more than 3  
times a week.  
How many people will be studied?  
We expect about 60 people to participate in this research study each year.   
What happens if I say yes, I want to be in this research?  
It is up to you to decide whether or not to participate.   
As a subject in this study, you will be asked to come to a research laboratory in BDH 169 at Arizona  
State University Tempe campus for each of the test sessions. On the day of first test session, you will  
receive a telehealth training kit which you can use from your own home for the training sessions. The  
home sessions with the experimenter will be conducted using a videoconferencing software. You are  
required to return the training kit to the experimenter when you attend the subsequent test session.  
Pre-Screening Procedures   

To determine if you can take part in the study, you will be asked about past injuries to your arm, 
your  hearing sensitivity, present seizure concerns, and heart conditions which contraindicate exercise 
related activities. You should not be pregnant during this study. You will also  be asked about your ability 
to participate in telehealth, including questions about the type of computer  and videoconferencing 
software you have access to. In addition, you will also be asked whether you  are comfortable and able 
to participate without assistance from a caretaker. You will also be asked to  complete a handedness 
questionnaire. This will tell us whether you are right- or left-hand dominant.   
Study Procedures   
You will be seated in a comfortable chair for all tasks and assessments. During the test sessions 
you  will have small recording devices called electrodes attached to your skin over several different  
muscles. These electrodes are similar to stickers but are specially designed to allow us to look at how  
you use your muscle to perform different tasks. In these sessions you may also have several small non 
invasive sensors attached to your hand and arm, they will be used to record the kinematic data of your  
arm and elbow.  
Similar to the test session, during the remote training sessions, you will be asked to be seated in 
your  most comfortable chair with a table in front of you, where you comfortably rest your arm. You may 
be  asked to put on an activity tracker on both wrists for the duration of the study. This will be used to  
record the amount of arm movements you make on a day-to-day basis. During the remote training  
session, you will be asked to put on the headphones included in the training kit. These headphones will  
be plugged into the smart phone device, also included in the kit. You will be asked to open an app on  
the phone that provides the experimenter access to conduct the telehealth training remotely.  
The experiment may consist of several tasks using your arm and hand. You will have adequate 
time to  practice these movements and will be allowed to rest in between trials and tasks if you become 
tired.   
Sometimes you may hear a loud, startling sound from the headphones during posturing and 
preparation  of movement. These sounds have been measured to ensure that no hearing damage or 
injury can occur.   
What happens if I say yes, but I change my mind later?  
You can leave the research at any time it will not be held against you. If you decide to leave the  
research, there will be no adverse consequences. If you stop being in the research, already collected  
data may not be removed from the study database.  Is there any way being in this study could be bad for 
me?  
Psychological risks:  
All the devices and equipment used in this research have been used in numerous of research 
studies  and proved to be safe. All precautions will be taken to minimize these risks. Acoustic stimulus 
may  cause temporary discomfort, fatigue and anxiety. If so, you can take a break or withdraw from the  
study.   
Physical risks:  

Muscle activity and body motion will be recorded using small electrodes placed on the surface of 
the  skin. The skin will be cleansed with alcohol and gently rubbed with a cloth before placing the 
electrodes on the skin. The skin may show some redness and minor irritation for a few hours after the  
completion of the experiment.  
Physical risks and discomforts expected in this study are dependent on your level of physical 
fitness.  In the days following your participation, you may develop muscle soreness that is common after  
exercise. Also, the activity tracker worn around your wrist for the duration or the study may cause  some 
slight skin irritation. However, this is like putting on a watch and has been designed to be worn  for long 
hours.   
Privacy risks:  
There is always a potential risk of loss of confidentiality. All data will be labeled with a research 
code  from which subject identification is not possible and only researchers will have access to the 
codes.  All data will be stored on a password-protected hard drive or in a locked cabinet in the 
laboratory.  
What happens to the information collected for the research?  
Efforts will be made to limit the use and disclosure of your personal information, including 
research  study and medical records, to people who have a need to review this information. We cannot 
promise  complete secrecy. Organizations that may inspect and copy your information include the IRB, 
other  representatives of this organization, and federal entities that are funding the research.   
What else do I need to know?  
If you agree to take part in this research study, we will compensate you for your time and effort, in the  
form of an eGiftCard - $100 for the five day testing & training period period and an additional  
$50  for the one-month follow-up session. We can provide up to $100 per day to cover transportation 
costs to testing sites.  
In some of the experiments, videotaping may be requested for scientific and professional 
purposes.  Upon your consent, the process of data collection and some experimental detail may be 
videotaped, but  no information in the video record would reveal your identity. The video record will be 
edited so that  your face will not be visible, and the video record will only be used for research purpose. 
You are also  able to stop the videotaping anytime during the experiment.  
  
I give my permission to the investigators to video tape the data collection process and use the  edited 
video recordings, made during the data collection, for professional and scientific purposes. In  these 
edited videos it will not be possible to see my face. Initial here _______  
 I am interested in participating in other studies on campus and I give my permission to the  investigators 
to give my contact information to other researchers who have currently approved IRBs  for stroke 
survivors. Initial here _______  
Who can I talk to?  

If you have questions, concerns, or complaints, or think the research has hurt you, contact the PI:   
Claire Honeycutt: cfhoneyc@asu.edu  
This research has been reviewed and approved by the Bioscience IRB (“IRB”). You may talk to them  at 
(480) 965-6788 or research.integrity@asu.edu if:  
• Your questions, concerns, or complaints are not being answered by the research team.  
• You cannot reach the research team.  
• You want to talk to someone besides the research team.  
• You have questions about your rights as a research participant.  
• You want to get information or provide input about this research.  
Signature Block for Capable Adult  
Your signature documents your permission to take part in this research.  
Signature of participant  
Date  
Printed name of participant  
Signature of person obtaining consent Date  
Printed name of person obtaining consent