Application of a Reimbursable Form of Constraint-Induced Movement Therapy for Upper Extremity Recovery Following Stroke: A Pilot Study
Phase: NA
Conditions: CVA (Cerebrovascular Accident), Stroke, Upper Extremity Paresis
Sponsor: University of Alabama at Birmingham

Protocol Title 
 
 
Study Protocol & Statistical Analysis Plan 
 
NCT05311384 
 
 
01/02/2023 
 
 
Sarah dos Anjos, PhD, OTD, MSc, OTR/L, Principal Investigator 
University of Alabama at Birmingham 
Birmingham, AL 35294 
 
 
 
 
 
 
 
 
 
 
 
 
 

1. STUDY PLAN 
 
Constraint-induced Movement Therapy (CIMT) is a family of techniques that has 
systematically applied intensive treatment daily over consecutive days, supervised 
motor training using a technique called shaping, behavioral strategies to improve the 
use of the affected limb in real life situations called a Transfer Package (TP), and the 
use of strategies to remind participants to use the affected extremity; including 
restraint of the non-affected arm. Studies have shown robust evidence on the effect 
of CIMT in increasing the amount and the quality of use of the paretic UE in daily 
situations of individuals with stroke. 
Despite strong evidence and acceptance in the scientific community, clinical 
application of ClMT has been challenging. Barriers for its implementation in clinical 
settings include time needed by therapists, other resources required and lack of 
payment for the services. With regards to therapists' time, in the traditional ClMT 
protocol, therapists supervised training for 3.5 hours daily (except for weekends) for 
a 10 consecutive weekdays period. This level of supervision in highly unusual for 
traditional rehabilitation clinical settings. The treatment schedule in also incompatible 
with most insurance reimbursement policies in the US, and in most cases, patients 
pay for the treatment privately (with little or no insurance reimbursement). Such 
practices severely limit the number of patients who have access to ClMT. Two lines of 
evidence have suggested that an alternative ClMT protocol may allow for the essential 
(or "Key") elements to be delivered in a schedule that better utilizes therapist time 
and is compatible with payment policies of many US insurance companies. One line 
of evidence comes from findings that indicate that the original 6-hour supervised 
training schedule could be shortened to as little as 2-hours/daily without a reduction 
in outcomes. Additional evidence comes from a study exploring the systematic 
addition and deletion of the traditional Cl therapy protocol elements indicated that 
when the transfer package was omitted, outcomes related to functional use were 
reduced by 50%. These findings were also verified by brain imaging studies conducted 
concurrently that revealed a much-reduced level of brain remodeling in those not 
receiving the transfer package. These findings highlight the potential effectiveness of 
the transfer package and continued functional training by the patient while away from 
clinical supervision. Therefore, the Keys treatment protocol was developed, providing 
a distributed schedule (1 to 4 times/ week over an 8-week period) instead of 
consecutively over a 12-day treatment period. Also, patients would be exposed to the 
behavioral component of the protocol, the transfer package, for an extended period 
(Figure 1). 
 
Figure 1. Keys treatment protocol schedule 
 

 
  
 
 
Project Design and Methods 
• Participants: 10 participants with chronic stroke were included in the pilot 
trial. Individuals were included if they (1) were age 18 years or older; (2) 
had a stroke at least 6 months prior to enrollment; (3) were able to 
demonstrate minimum movement criteria of more-affected UE including 10 
degrees of wrist extension (starting from a fully flexed position), 10 
degrees of thumb abduction, and 10 degrees of extension of two additional 
fingers at all joints; (4) scored less than 2.5 on the Motor Activity Log 
(MAL); (5) achieved score of 24 or higher on the Mini Mental State 
Examination (MMSE); (6) demonstrated the ability to comprehend and 
answer the Motor Activity Log (MAL) questions; and (7) had not received a 
botulin toxin injection or adjustments in anti-spasticity drug regimens within 
3 months of treatment. Sensory deficits were not an exclusion. Individuals 
who were not fluent in English were excluded from the study. 
• Outcome Measures: Aim 1 will be assessed using the MAL (Arm use), 
WMFT (Arm capacity), SIS (Quality of Life), ZDS (Depression) and COPM 
(Functional activity preference, ability and satisfaction). All measures will 
be administered immediately pre­ treatment, at the end of the 4th week of 
the intervention (middle of treatment), and at post-treatment. The MAL, 
SIS, ZDS, and the COPM will also be administered at 3 months post-
intervention by telephone. 
• Intervention: All participants will receive the Keys intervention protocol 
over an 8-week intervention period. Specific Cl therapy strategies will be 
delivered as previously described' except for the following 
modifications: 1) supervised training for 1.5 hours (i.e., 2 shaping tasks), 
gradually decreasing the number of weekly session over the course of 8 

weeks with 4 days/week for the first 4 weeks, 2 days/week for weeks 5 
and 6, and 1 day/week for weeks 7 and 8; 2) participants will use the 
restraint mitt on their less-affected UE for most of their waking hours for 
the 8 week period; 3) transfer package methods will be modified to 
accommodate the longer time period between clinic visits; and 4) 
participants will be asked to independently perform additional 
movement training for 30 minutes each day at home. 
 
2. STATISTICAL PLAN 
 
Demographic data including age, ethnicity or race, type of stroke, chronicity, 
affected side and pre-morbid handedness are reported as frequence (percentage), 
mean and full range.  All outcome measures, as well as their units, when each one was 
administered, and analysis is described below. 
 
Outcome 
measures 
Unit 
Administration 
time points 
Reported 
as 
Analysis 
MAL AOU 
Score 
on a 
scale 
Pre-, during, 
post-treatment 
and follow up 
Mean and 
full range 
Difference between pre-treatment 
and the other data points. 
Comparison with the MCID 
MAL QOM 
Score 
on a 
scale 
Pre-, during, 
post-treatment 
and follow up 
Mean and 
full range 
Difference between pre-treatment 
and the other data points. 
Comparison with the MCID 
COPM 
Performance 
Score 
on a 
scale 
Pre-, during, 
post-treatment 
and follow up 
Mean and 
full range 
Difference between pre-treatment 
and the other data points. 
Comparison with the MCID 
COPM 
Satisfaction 
Score 
on a 
scale 
Pre-, during, 
post-treatment 
and follow up 
Mean and 
full range 
Difference between pre-treatment 
and the other data points. 
Comparison with the MCID 
WMFT - 
performance 
time (s) 
Time in 
seconds 
Pre-, during, 
post-treatment  
Median 
and full 
range 
Difference between pre-treatment 
and the other data points. 
Comparison with the MCID 
WMFT – 
Functional 
Ability Scale 
Score 
on a 
scale 
Pre-, during, 
post-treatment  
Mean and 
full range 
Difference between pre-treatment 
and the other data points. 
SIS - Physical 
Score 
on a 
scale 
Pre-, during, 
post-treatment 
and follow up 
Mean and 
full range 
Difference between pre-treatment 
and the other data points. 
Comparison with the MCID 
SIS - Memory 
Score 
on a 
scale 
Pre-, during, 
post-treatment 
and follow up 
Mean and 
full range 
Difference between pre-treatment 
and the other data points. 
Comparison with the MCID 

SIS - Mood 
Score 
on a 
scale 
Pre-, during, 
post-treatment 
and follow up 
Mean and 
full range 
Difference between pre-treatment 
and the other data points. 
Comparison with the MCID 
SIS - 
Communication 
Score 
on a 
scale 
Pre-, during, 
post-treatment 
and follow up 
Mean and 
full range 
Difference between pre-treatment 
and the other data points. 
Comparison with the MCID 
SIS - ADLs 
Score 
on a 
scale 
Pre-, during, 
post-treatment 
and follow up 
Mean and 
full range 
Difference between pre-treatment 
and the other data points. 
Comparison with the MCID 
SIS - Mobility 
Score 
on a 
scale 
Pre-, during, 
post-treatment 
and follow up 
Mean and 
full range 
Difference between pre-treatment 
and the other data points. 
Comparison with the MCID 
SIS - Hand 
function 
Score 
on a 
scale 
Pre-, during, 
post-treatment 
and follow up 
Mean and 
full range 
Difference between pre-treatment 
and the other data points. 
Comparison with the MCID 
SIS - 
Participation 
Score 
on a 
scale 
Pre-, during, 
post-treatment 
and follow up 
Mean and 
full range 
Difference between pre-treatment 
and the other data points. 
Comparison with the MCID 
SIS - Recovery 
Score 
on a 
scale 
Pre-, during, 
post-treatment 
and follow up 
Mean and 
full range 
Difference between pre-treatment 
and the other data points. 
Comparison with the MCID 
ZDS 
Score 
on a 
scale 
Pre-, during, 
post-treatment 
and follow up 
Mean and 
full range 
Difference between pre-treatment 
and the other data points.  
MAL = Motor Activity Log; AOU = amount of use; QOM: quality of movement; COPM = 
Canadian Occupational Performance Measure; WMFT =Wolf Motor Function Test; SIS 
= Stroke Impact Scale; ZDS = Zung Depression Scale; MCID = Minimal Clinically 
Important. 

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CONSENT FORM TO BE PART OF A RESEARCH STUDY
Title of Research:
Application of a Reimbursable Form of Constraint Induced 
Movement Therapy for Upper Extremity Recovery Following Stroke: 
A Feasibility Study
UAB IRB Protocol #:
IRB-300008977
Principal Investigator:
Sarah Dos Anjos, OT, PhD
Sponsor:
Center for Engagement in Disability Health and Rehabilitation 
Sciences (CEDHARS) pilot funding. 
General Information
You are being asked to take part in a research study. This research study is 
voluntary, meaning you do not have to take part in it. The procedures, 
risks, and benefits are fully described further in the consent form.
Purpose
The purpose of the study is to investigate 1) if a distributed protocol of 
Constraint-Induced Movement Therapy is feasible, and 2) the effects of 
this protocol in the use of your more affected arm (e.g. the arm affected by 
the stroke).
Duration & Visits
You will be in this study for 8 weeks. Also, you will be asked to come for 
one screening visit, 4 assessments visits that will last approximately 3h, 
each.
Overview of 
Procedures
This study will include 22 sessions distributed in 8 weeks of exercises for 
your arm that was affected by the stroke, and the administration of a 
questionnaire. Each session will last 1.5h. You will also be asked to perform 
tasks at home to reinforce what has been emphasized in the laboratory. 
You will be asked to come for a screening visit, and if you are included, 
there will be 4 evaluation sessions, pre-treatment, 4 weeks after the 
treatment had started, after the treatment, and 3 months after the end of 
the treatment project.
After the end of the treatments, one of the questionnaires will be 
administered weekly for the first months after the end of the treatment by 
phone with two additional questionnaires asked at the fourth week after 
treatment.
Risks
The most common risks include muscle fatigue and soreness from the 
exercises you will perform during your visits to the laboratory and at home. 
Benefits
You may or may not benefit from the study. You may gain valuable 
information about how you move your affected arm as well as activities 
you can do at home using your affected arm.
Alternatives
If you do not want to take part in the study, your alternative is not to 
UAB IRB
Approved
02-Jan-2023

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participate. You may stop at any time.
Purpose of the Research Study
We are asking you to take part in a pilot research study. The purpose of the pilot study is to evaluate 
1) whether a structure of the Constraint-Induced Movement Therapy (CIMT) protocol is feasible, and 
2) its effect on motor function and use of the arm affected by the stroke. The new therapy is named 
Keys Treatment. This therapy includes all of the components in CIMT but is delivered over a 
distributed schedule in fewer hours each day. CIMT involves repeating intensive exercises with your 
impaired arm (the arm more-affected after stroke) and using your impaired arm for everyday 
activities.  In numerous studies of CIMT at UAB and in research studies around the world, it has been 
found that CIMT has helped improve motor function of the impaired arm of stroke patients. 
Study Participation & Procedures
Before participating in the research study, you will be examined by a team member who specializes in 
physical rehabilitation. They will determine if you are a good fit for the study. They will ask you 
questions about your medical history, take vital signs, and measure your ability to move your arms. 
The results of the evaluations can disqualify you from participating in the research if you do not meet 
the minimum requirements. If your arm function or health status changes after this evaluation, you 
may be dismissed from participating in the study. Therefore, you are encouraged not to change how 
you use your impaired arm between the screening evaluation and the start of treatment. If you 
qualify for and agree to join this study, you will be enrolled in the study. 

You will come in for initial screening, pre-treatment testing, periodic testing, and final testing.

Treatment will occur for up to 1.5 hours each session over 8 weeks with 4 days per week for 
Weeks 1,2,3, and 4; then treatment tapers to 2 days per week for Weeks 5 and 6, then 1 day 
per week for Weeks 7 and 8.  

On the last day of treatment, a face-to-face individual interview will be conducted. The 
interview will be audio recorded and transcribed verbatim afterwards. The interview 
questions will explore your perceptions and opinions regarding the treatment protocol you 
participated in.

The research team will administer one questionnaire once a week for 4 weeks over the phone 
or through an online link to an electronic form. 

If you are entered and complete the entire study, you will be in the study for approximately 5  
months, including training sessions, and evaluation visits.
Before the treatment period begins, your ability to move your arms will be tested and several 
questionnaires and motor tests will be given. Testing will take place about one week before 
treatment starts. The first day you participate in the study, researchers will ask you to complete 
testing questionnaires which measure your use of the impaired arm at home, ability to think, opinion 
about the treatments you have received in the past, and quality of life. You will also be asked to 
complete motor testing that measures the speed and quality of your arm movements. The 
questionnaires and motor testing will include: 

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 Motor Activity Log (MAL; measures how well and how much the impaired arm is used in your 
everyday life) 
 Canadian Occupational Performance Measure (COPM; rating how well and how satisfied you are 
for tasks that are important to you) 
 Wolf Motor Function Test (WMFT; arm motor skills) 
 Participant Opinion Survey (expectations about and satisfaction with treatment)
Stroke Impact Scale (SIS; quality of life)
 Mini-Mental State Examination (MMSE; thinking skills) 
 Zung Depression Inventory (ZDS; mood)
Some of the questionnaires might be administered by telephone or mail. Some of the tests will be 
videotaped. 
Treatment will begin on your third visit to the laboratory.  Sessions will last up to 1.5 hours each day 
to complete the treatment procedures that will include: 
 arm training (personalized to focus on your needs) 
 arm training using everyday activities 
A portion of each session, 15 minutes on average, will be spent going over a set of techniques that 
help you carry over improvements from the laboratory to the home. In addition, at the beginning of 
treatment, you will be evaluated for any specialized equipment, such as a built-up spoon or spill proof 
mug that will help maximize the potential for improved use of the arm. These aids may change as 
needed throughout the treatment. 
The therapy will also involve wearing a safety mitt about 90% of the time during the hours of the day 
that you are awake. The mitt is so that you do not use your stronger arm. You will remove the mitt 
before going to bed, and you will put it on in the morning. You will also be able to remove the mitt to 
carry out necessary bathroom functions and whenever it is not safe to keep it on. While your 
unimpaired arm is in the mitt, you are to make every effort to use your impaired arm as much as 
possible. 
You will be asked to do some homework when out of the treatment setting. You will be asked to: 
 sign an agreement to carry out the homework and other aspects of the training 
 do some homework assignments when out of the treatment setting 
 keep a daily home diary, and 
 talk to your therapist about problems that you face in implementing the homework during 
treatment, during the calls that will be conducted weekly for 4 weeks after the end of the protocol. 
After you complete treatment, you will repeat the testing you did before treatment, i.e., motor 
testing and questionnaires. In addition, The MAL, SIS, COPM, and ZDS will also be administered at 
3 months after your treatment by telephone. If you live with a family member or have a 
professional caregiver, they may be asked to help you to participate in this research study. If you 
are asked to wear a mitt at home, your family member or caregiver will be asked to be present 
and assist you when you practice using your impaired arm. 
Risks and Discomforts

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While your less-affected arm is restrained you may feel anxious and frustrated. These feelings may be 
stressful. However, researchers will watch you closely to make sure you do not get hurt. There is a 
low risk that you may be cut or bruised while performing the training tasks. The therapists working on 
this study have extensive experience with designing safe training tasks, and the risk is low. You may 
also feel tired or fatigued during training for your impaired arm or may experience pain. The therapist 
will monitor your activity levels and provide rest breaks as needed to prevent feelings of fatigue or 
pain from becoming excessive. The only small chance of serious injury may occur if loss of balance 
occurs when wearing the safety mitt. The mitt leaves the less-affected arm free to swing to maintain 
balance while walking. If you did fall, it would be available for defense. In case of emergencies or in 
situations where you feel at risk of falling, you can remove the safety mitt -- but only under those 
circumstances. Otherwise, you are to keep the padded mitt on for the agreed-upon period. You may 
risk being recognized from the video recordings done for this study by the individuals who will rate 
your motor performance. This is an unlikely event. Moreover, these individuals will be trained to 
respect the confidentiality of study participants. You may risk disclosure of the information collected 
for this study, if, for example, a hacker breaks into the computer systems where the study data are 
stored. This is an unlikely event because of the information collected for this study will be stored 
securely.
Benefits
You may not benefit directly from taking part in this study. However, this study may improve 
spontaneous use of your more-affected arm in the life setting, through using a safely performed 
motor intervention. Your participation may provide valuable information to the medical community 
about the treatment of stroke. 
Alternatives
Your alternative is to not participate in the study. 
Confidentiality and Authorization to Use and Disclose Information for Research Purposes
Federal regulations give you certain rights related to your health information. These include the right 
to know who will be able to get the information and why they may be able to get it. The principal 
investigator must get your authorization (permission) to use or give out any health information that 
might identify you.
What protected health information may be used and/or given to others?
All medical information, including but not limited to information and/or records of any diagnosis or 
treatment of disease or condition, which may include sexually transmitted diseases (e.g., HIV, etc.) or 
communicable diseases, drug/alcohol dependency, etc.; all personal identifiers, including but not 
limited to your name, social security number, medical record number, date of birth, dates of service, 
etc.; any past, present, and future history, examinations, laboratory results, imaging studies and 
reports and treatments of any kind, including but not limited to drug/alcohol treatment, 
psychiatric/psychological treatment; financial/billing information, including but not limited to copies 
of your medical bills; any other information related to or collected for use in the research study, 

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regardless of whether the information was collected for research or non-research (e.g., treatment) 
purposes; records about any study drug you received or about study devices used; and consent forms 
from past studies that might be in your medical record.
A description of this clinical trial will be available on www.ClinicalTrials.gov, as required by U.S. Law. 
This website will not include information that can identify you. At most, the website will include a 
summary of the results. You can search this website at any time.
Who may use and give out this information?
Information about your health may be used and given to others by the principal investigator and 
staff. They might see the research information during and after the study.
Who might get this information?
All individuals/entities listed in the informed consent document(s), including but not limited to, the 
physicians, nurses and staff and others performing services related to the research (whether at UAB 
or elsewhere). Your information may also be given to the sponsor of this research. “Sponsor” includes 
any persons or companies that are working for or with the sponsor, or are owned by the sponsor, or 
are providing support to the sponsor (e.g., contract research organization).
Information about you and your health which might identify you may be given to:

The Office for Human Research Protections (OHRP)

The UAB Institutional Review Board (IRB). An IRB is a group that reviews the study to protect the 
rights and welfare of research participants.

The UAB Center of Engagement in Disability health and Rehabilitation Sciences (CEDHARS)
Why will this information be used and/or given to others?
Information about you and your health that might identify you may be given to others to carry out 
the research study. The sponsor will analyze and evaluate the results of the study. In addition, people 
from the sponsor and its consultants will be visiting the research site. They will follow how the study 
is done, and they will be reviewing your information for this purpose.
What if I decide not to give permission to use and give out my health information?
By signing this consent form, you are giving permission to use and give out the health information 
listed above for the purposes described above. If you refuse to give permission, you will not be able 
to be in this research.
May I review or copy the information obtained from me or created about me?
You have the right to review and copy your health information. However, if you decide to be in this 
study and sign this permission form, you will not be allowed to look at or copy your information until 
after the research is completed.
May I withdraw or revoke (cancel) my permission?
Yes, but this permission will not stop automatically. The use of your personal health information will 
continue until you cancel your permission.

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You may withdraw or take away your permission to use and disclose your health information at any 
time. You do this by sending written notice to the study doctor. If you withdraw your permission, you 
will not be able to continue being in this study.
When you withdraw your permission, no new health information which might identify you will be 
gathered after that date. Information that has already been gathered may still be used and given to 
others. This would be done if it were necessary for the research to be reliable.
Is my health information protected after it has been given to others?
If you give permission to give your identifiable health information to a person or business, the 
information may no longer be protected. There is a risk that your information will be released to 
others. Including others outside of UAB, without your permission.
Voluntary Participation and Withdrawal
Whether or not you take part in this study is your choice. There will be no penalty if you decide not to 
be in it. If you decide not to be in the study, you will not lose any benefits you are otherwise owed.
You are free to withdraw from this study at any time. Your choice to leave the study will not affect 
your relationship with this institution. Contact the study PI, Dr. Sarah dos Anjos if you want to 
withdraw from the study.
You may be removed from the removed from the study without your consent if the sponsor ends the 
study if the study PI decides it is not in the best interest of your health, or if you are not following the 
study rules. 
Cost of Participation
There will be no costs to you for participation in the research. 
Payment for Participation
There is no compensation for participation in this study. 
Payment for Research-Related Injuries
UAB has not provided for any payment if you are harmed as a result of taking part in this study. If 
such harm occurs, treatment will be provided. However, this treatment will not be provided free of 
charge.
New Findings
You will be told by the Dr Sarah Dos Anjos or the study staff if new information becomes available 
that might affect your choice to stay in the study. 

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Optional Research
We would like your permission to keep your private information (data containing personal 
information) collected in this study for future research. We would like your permission to contact you 
for future research. The future research may be similar to this study or may be completely different. 
Your private information will be stored indefinitely or until used.
Your private information will be labeled with a code that only the study staff can link back to you. 
Results of any future research will not be given to you or your doctor. 
You can take part in this study even if you decide not to let us keep your private information for 
future research. You can decline participation in any future research you are contacted for. 
If you give us permission now to keep your private information and, you can change your mind later 
and ask us to destroy it. However, once we have analyzed your private information and data, we may 
not be able to take it out of our future research.
We may share your private information, so that others can use it in their research. Their research 
may be similar to this study or may be completely different. Once we have shared your private 
information with other researchers, we will not be able to get it back.
Future research use of your private information will be conducted in compliance with applicable 
regulatory requirements.
You will not find out the results of future research on your private information. Allowing us to do 
future research on your private information will not benefit you directly.
The private information used for future research may be used for commercial profit. There are no 
plans to provide financial compensation to you should this occur.
Initial your choice below:
___ I agree to allow my private information to be kept and used for future research 
 
___ I do not agree to allow my private information to be kept and used for future research.
___ I agree to be contacted for participation in future research
___ I do not agree to be contacted for participation in future research
Questions

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If you have any questions, concerns, or complaints about the research or a research-related injury 
including available treatments, please contact the study doctor. You may contact Dr. Sarah Dos Anjos 
at (205) 934-7323 or smanjos@uab.edu.
If you have questions about your rights as a research participant, or concerns or complaints about the 
research, you may contact the UAB Office of the IRB (OIRB) at (205) 934-3789 or toll free at 1-855-
860-3789. Regular hours for the OIRB are 8:00 a.m. to 5:00 p.m. CT, Monday through Friday.
Legal Rights
You are not waiving any of your legal rights by signing this consent form.
Signatures
Your signature below indicates that you have read (or been read) the information provided above 
and agree to participate in this study. You will receive a copy of this signed consent form.
Signature of Participant or Legally Authorized Representative
Date
Signature of Person Obtaining Consent
Date