In Vivo Three-Dimensional Determination of Osteoarthritis Brace Effectiveness
Phase: NA
Conditions: Osteoarthritis, Knee
Sponsor: The University of Tennessee, Knoxville

20191576 
 
 
 
 
In vivo Three-Dimensional Determination of 
OA Brace Effectiveness 
IRB Conditions 
Satisfied at the Protocol 
Level 
Jun 24, 2019 
 
Richard D Komistek, PhD 
University of Tennessee 
1506 Middle Drive 
310 Perkins Hall 
Knoxville, TN 37996 
Phone: (865) 974-4159 
Fax: (865) 946-1787 
Email: rkomiste@utk.edu 
 
In vivo knee kinematics will be assessed for 20 subjects that have been clinically diagnosed with 
substantial unicompartmental osteoarthritis (OA) by one of the surgeons of Colorado Joint 
Replacement; this is the location from which participants will be recruited. 
Enrollment will be increased to 24 subjects to account for any dropouts. Medial joint space 
narrowing will be clinically assessed in all patients on standing anteroposterior radiographs. The 
objective of this study will be to analyze subjects with symptomatic unicompartmental 
osteoarthritis under in vivo dynamic, weight-bearing conditions using video fluoroscopy to 
determine if present-day OA knee braces provide separation of the femoral condyle from the 
tibial plateau, thus avoiding excessive loads on the degenerative compartment. 
 
The study will be submitted to Western IRB (WIRB); the University of Tennessee’s IRB and 
Centura Health/Catholic Health Initiatives (for Colorado Joint Replacement/Porter Adventist 
Hospital) have waived oversight to WIRB. The required Reliance Agreements will be included 
with this submission to WIRB. 
 
We will use the following inclusion criteria to recruit participants for this study: 
1. Must be a patient of Colorado Joint Replacement. 
2. Must be diagnosed with marked unicompartimental degenerative joint space narrowing. 
3. Bilateral subjects may not be included in the subject population. 
 
Exclusion criteria: 
1. 
Pregnant, potentially pregnant or lactating females. To satisfy radiation protocol, each 
female subject will be asked if she is pregnant, or possibly could be pregnant. A 
pregnant person will not be allowed to participate in the study. 
2. 
Subjects who are unable to perform normal walking. 
3. 
Subjects who are unwilling to sign Informed Consent/ HIPAA documents. 
4. 
Does not speak English. 
 
Investigators 
Richard D. Komistek, Ph. D. (PI) 
Douglas A. Dennis, MD (Co-PI) 
Jason Jennings, MD (Sub-I) 
Michael T. LaCour, Ph. D. (Sub-I) 
Jacob Elkins, MD (Sub-I) 
Lindsay Kleeman-Forsthuber, MD (Sub-I) 
IRB Approved at the 
Protocol Level 
Jul 11, 2019

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Study locations 
Subject Recruitment will take place at Colorado Joint Replacement: 
Colorado Joint Replacement 
2535 S Downing St., Suite 100 
Denver, CO 80210 
(720) 524-1367 
 
Fluoroscopic exams, ultrasound exams and CT exams will be performed on 
all 20 (or possibly 24) subjects at: Porter Adventist Hospital 
2525 S Downing St. 
Denver, CO 80210 
(303) 778-1955 
 
Satellite sites: 
Analysis will take place at the University of Tennessee’s Center for Musculoskeletal Research 
laboratories: 
Science and Engineering Research Facility 
1414 Circle Dr. 
Knoxville, TN 37996 
 
CMR administrative offices: 
310 Perkins Hall 
1506 Middle Dr. 
Knoxville, TN 37996 
 
Recruitment 
Patients of Colorado Joint Replacement in Denver, Colorado will recommend eligible subjects 
for recruitment who have been clinically diagnosed to have marked unicompartimental 
degenerative joint space narrowing. Since there are no inclusion criteria other than being a 
patient of Colorado Joint Replacement and having unicompartmental OA, review of patient 
medical files prior to contacting about participation is not necessary. No inclusion/exclusion 
checklists will be used to ensure eligibility since no other criteria must be met other than being a 
patient of Colorado Joint Replacement, having the unicompartimental degenerative joint space 
narrowing, being able to speak English and perform normal walking. The surgeons of Colorado 
Joint Replacement will be aware of which of their patients have this joint condition. Even though 
a HIPAA waiver for recruitment will not be necessary, patient medical files will need to be 
accessed in order to acquire contact information for each potential subject. 
 
Ms. Roseann Johnson will contact the patients to explain the study using an approved script and 
inquire as to whether or not they are interested in participating. A partial waiver of HIPAA has 
been included for this. The surgeons of Colorado Joint Replacement may also bring the study to 
patients’ attention during regular office visits and will use language similar to that in the script. 
If a patient is agreeable to participate, s/he will be scheduled to visit Porter Adventist Hospital 
on the day of data collection. On this scheduled day, UT researchers will travel to Porter to 
collect the kinematic data of participants’ knees under fluoroscopic surveillance using a C-arm 
fluoroscopic unit while subjects perform normal treadmill walking in the frontal plane. The 
fluoroscopic images will be stored on password protected computer workstations for subsequent 
analysis. 

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Data Collection 
Fluoroscopy 
On the scheduled day of data collection, here will be at least two UT researchers present (which 
could also include the PI), as well as a study PI, (Drs. Komistek, Dennis; Jennings, Elkins, 
Kleeman-Forsthuber, LaCour [Sub-Investigators]) to conduct the fluoroscopic evaluation. Each 
subject will be asked to perform gait without the assistance of an offloading brace (Figure 1a). 
Then, each subject will be fitted with a Breg, off-the-shelf OA brace and will perform normal 
gait while under fluoroscopic surveillance (Figure 1b). To ensure each brace was fitted properly, 
Breg will be asked to send either a sales representative or an engineer to the evaluation site. 
Therefore, the sales representative or engineer will be asked to fit their brace on each of the 
subjects. This individual will sign a pledge of confidentiality. 
 
a 
b 
Figure 1. Subject on a treadmill perform gait without a brace (a) and with a brace (b). 
 
A Radiation Technician (RT) employed by Porter Adventist Hospital will perform the actual 
fluoroscopy procedure, following the subjects’ OA knee with the unit as the activity is performed 
with and without the OA brace; only the knee joint (from the fluoroscopy machine) will be 
recorded on the fluoroscopy footage. The UT researchers, graduate research assistants (GRAs), 
which may include any of the following - Garett Dessinger, Jarrod Nachtrab, Milad Khasian, 
Lauren Smith, Seth Coomer – will be present, although they will not perform the actual 
fluoroscopy procedure. They will be present during the fluoroscopy procedure to walk subjects 
through the activities, answer any questions that may arise, ensure data collection equipment is 
set up as needed and serve as consultants to the RT. 
 
Any of these UT individuals, or study staff from Colorado Joint Replacement, will consent the 
participants. They will meet with each potential participant individually to make sure s/he has 
been properly informed of the procedures and to help with any of the IC form. CMR researchers 
will inform all subjects that they do not have to participate and are free to leave if they wish and 
will answer any questions subjects may have about the study. Participation is entirely voluntary. 

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Participants will be asked to practice the activity to ensure they can comfortably complete it and 
experience no pain with the fluoroscopy machine off (no radiation). The practice portion of the 
data collection without radiation will not be video-recorded. 
 
Multiple trials of each activity may be conducted to ensure usable images have been acquired to 
complete the study. Radiation time will be kept as low as reasonably achievable (ALARA) and 
will not exceed two minutes. The RT will start the fluoroscope just prior to the subject beginning 
the activity trial and will stop the fluoroscope immediately after the subject completes each 
activity trial to ensure that the subject is not exposed during idol periods. On-time will be 
recorded on the subject’s IC, as well as any output the fluoroscopy unit is able to provide. 
 
In addition to fluoroscopy video, subjects will be videotaped from the shoulders down (to 
maintain subject anonymity) while performing the activities (live feed perspective). The speed 
level of each trial will be based on the comfort level of the subject. One of the researchers will be 
ready and in close proximity to assist each subject in case the participant requires help. This 
precaution will be practiced for all participants, regardless of physical wellbeing, age or prior 
results; no assumptions will be made as to any participant’s capabilities. The participant will be 
allowed to rest as necessary and be instructed to stop the activity at the first sign of pain. 
 
The fluoroscopic and video footage for the study activities will be stored on digital video files on 
a secure computer workstation and stored securely by UT researchers. It will then be uploaded 
onto the secure CMR database by these researchers. Once the data has been uploaded, identifiers 
are removed from the data automatically by the database, and a study and subject-specific 
identifier will be assigned to each subject. 
 
JointVue three-dimensional ultrasound 
Since the skeletal geometry is different for every person, computer aided design (CAD) models 
of the femur and tibia will be created for each specific subject. In order to create these CAD 
models, each subject will be asked to undergo a three-dimensional (3D) ultrasound using the 
JointVue proprietary software to reconstruct 3D femoral and tibial bones (Figure 2). A 
representative from JointVue will be present during data collection to conduct the ultrasound 
procedure in order to create the CAD models. This individual will sign a statement of 
confidentiality. 
 
Study data will then be uploaded onto a secure server that University of Tennessee researchers 
will use to conduct the kinematic analysis using a model-fitting approach, the relative pose of 
knee implant components will be determined in 3D from a single-perspective fluoroscopic image 
by manipulating a CAD model in 3D space. 
 
Using a model-fitting technique, the 3D bones will be overlaid onto the fluoroscopic images to 
determine amount of medial OA offloading. Successive fluoroscopic images of each subject’s 
stance phase, with and without the OA brace, will be downloaded to a computer. Images will be 
captured at five instances during stance-phase of gait: heel strike, 33% of stance phase, mid- 
stance, 66% of stance-phase and at toe-off. A comparative analysis will be conducted for each 
subject while wearing the OA brace and with their non-braced test. Then, the amount of medial 
condylar separation will be assessed for each subject. 

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Figure 2. Example of 3D bone creation. 
 
CT Scan 
Participants will be asked to schedule a CT scan at Porter Adventist Hospital at their convenience 
within 1 month of the initial data collection day.  To ensure subject safety, CT will be limited to 
the affected knee and the rest of patient’s body will be protected from radiation with lead 
protection.  The CT scan will be limited to the study knee and will image 6 inches distal on the 
tibia and 6 inches proximal on the femur. 
 
Private Health Information/Medical Record Data 
It is not anticipated that the subjects’ medical files should need to be accessed for any PHI for the 
study for recruitment or for the conduct of the study itself. However, contact information from 
patient files will be acquired for inquiring as to whether or not patients would be willing to 
participate. The only subject-specific data that will be necessary will be measurements of medial 
condyle separation from the medial tibial plateau for each subject with and without a brace. 
Researchers will acquire the measurements with the brace while they are conducting the data 
collection. Researchers may also acquire the subjects’ medial condyle separation without the 
brace while they are present for data collection. However, if this is not possible or time does not 
permit, Colorado Joint Replacement staff may send that information to UT researchers via secure 
transfer (e.g., UT Vault). 
 
The subject data – fluoroscopy frames, video footage and ultrasound– will be uploaded and 
stored on CMR’s secure server for use in this and future studies (if participant permission is 
obtained via IC) by the researcher(s) who attend data collection or appointed by Dr. Komistek. 
Once data has been uploaded, the database automatically removes subject identifiers and assigns 
an ID for each subject. Only these files of de-identified data are now available for researchers to 
review and analyze. Only Dr. Komistek, Dr. LaCour and Garett Dessinger have access to the 

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identifiable data that was originally uploaded by the GRA, as it remains in a password-protected 
portion of the secure server. Only Dr. LaCour and Mr. Dessinger can grant access to this 
identifiable password- protected portion of the database by changing a user's level of 
authentication with different privilege levels. 
Researchers would like to retain this study data in our secure database so as to continue to add 
relevant, current data to our digital collection to help us work with manufacturers in the future to 
create better orthopaedic products. Participants will be asked if their study data may remain a 
part of the CMR data collection for use in future studies in the IC. Likewise, should a subject 
choose to withdraw from the study, s/he will have the option as to whether or not data collected 
from them at the point of withdrawal may be used for data analysis or if their information should 
be destroyed from CMR records; subjects choosing to withdraw will be asked to complete a 
Revocation of Consent wherein they may indicate their preference regarding the data collected 
from them. 
 
On the day of data collection, the list of patient names will be given to UT researchers and the 
researchers will generate subject-specific identifiers for each participant. A table will be 
generated for this study, indicating the participant’s name and generated ID number; this table 
with subject names and corresponding ID numbers will be provided to Colorado Joint 
Replacement staff, so the staff will be aware of which identifier is linked with each subject. If 
necessary (i.e., time not permitting during data collection; researchers unable to collect 
measurement), Colorado Joint Replacement staff may relate the measurements of medial condyle 
separation from the medial tibial plateau for each subject without a brace securely to UT 
researchers via the UT Vault https://vault.utk.edu/. 
 
SPECIFIC RISKS AND PROTECTION MEASURES 
 
1. Fluoroscopic Procedures 
As with every clinical study, there may be some risks. However, doses of radiation exposure 
received will be much lower than those known to produce detectable health effects. Previously 
reported literature shows that fluoroscopy-based procedure (angiography) on the lower limb 
result in a typical effective dose of 0.83 mSv per min (0.083 rem per min) (Verdun 1). Mettler, et 
al. have reported that the typical effective dose for a conventional knee procedure is 0.005 mSv 
(0.0005 rem)2. According to either estimate, the additional risk of a fluoroscopic procedure 
involving the knee ranges between "Negligible" to "Low" for a 2 minute exam (Verdun). A 
previous fluoroscopy TKA study conducted at another hospital with a 2 minute on-time limit 
shows that the average effective dose was 0.14 mSv (0.0014 rem) with a maximum dose of 0.27 
mSv (0.027 rem). The additional risk for all subjects in this previous study would be considered 
"Negligible." To account for subject variability and differences in imagining techniques, all 
subjects enrolled in this study will receive less than 2.0 rem. 2.0 rem is considered "Low" risk. It 
is unlikely that anyone in this study will approach the 2.0 rem limit. Since the fluoroscopy data 
will be collected in one session, there will only be one day in which the participants will be 
exposed to this amount of radiation. 
 
2. CT Scan 
In addition to the radiation exposure from the fluoroscopy procedure, all subjects will be 
exposed to radiation from the CT scan of the knee (which is considered an “extremity”), 
estimated at 0.01 rem, according to the American Nuclear Society’s Radiation Dose Chart, 

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http://www.ans.org/pi/resources/dosechart/ (Attachment 4). The radiology department at Porter 
Adventist hospital uses a software program call Caredose that automatically keeps the dose as 
low as possible on all CT exams.  Insofar as the amount of time for the CT scans taking place, 
we estimate approximately 30 minutes for the exam itself. 
 
In conclusion, a participant who will be fluoroscoped for less than two minutes will be exposed 
to a maximum amount of only 2.0 rems of radiation. This means that the maximum total 
exposure rate will be less than 2.0 rems per subject for the entire experiment. The participant's 
knee joint will be fluoroscoped using negligible to low risk levels of radiation according to 
published literature. 
 
The participant has the right to stop the procedure at any time; researchers or the RT can end the 
procedures at any time if they feel the participant is at risk, but the participant can choose to 
remain in the study if s/he feels that there is no risk to her/his surgical procedure or 
recuperation. 
 
3. Participant Confidentiality 
The investigators will ensure subject confidentiality to the extent that is permissible by law is 
maintained throughout the study and after. Researchers not notated as Investigators of this study 
that have access to subjects during data collection will sign pledges of confidentiality. Complete 
confidentiality cannot be guaranteed. 
 
Computer Database 
As noted, on the day of data collection, the list of patient names will be given to UT researchers 
and researchers will generate subject-specific identifiers; Colorado Joint Replacement staff will 
be provided with this list of subject names and corresponding generated identifiers. These 
assigned identifiers will be uploaded into an excel spreadsheet created by UT researchers. 
Colorado Joint Replacement staff will be aware of each subject’s respective identifier from the 
table provided to them on the day of data collection after UT researchers generate the subject- 
specific identifiers 
 
Researchers present during data collection or appointed by Dr. Komistek will upload the subject 
data, including fluoroscopy, video and ultrasound, into the CMR digital data collection. 
Consequently, student researchers in CMR who assist in data analysis cannot access subject- 
specific information. All participant queries (lookups) generate the participant identification 
number and no subject identifiers. No identifiable images exist in the database. This study data 
will be kept indefinitely on the secure CMR database for possible future research (with the 
permission of each participant – requested in the IC). In the case of participant withdrawal from 
the study, the Revocation of Consent that the participant will be asked to complete requests that 
the participant indicate whether or not data collected prior to withdrawal may be used for data 
analysis purposes, or if it should be removed from the CMR data collection completely and 
destroyed. 
 
Hard Copy 
In compliance with HIPAA regulations, all participants will have their identities withheld from 
all public files. Individuals not indicated as Investigators below will have access to participant 
information and they will sign pledges of confidentiality. The personnel in the following list will 
have access to participant study data: 

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List of Persons Involved in Research: 
 Dr. Richard Komistek, PI, UT Professor, Biomedical Engineering 
 Dr. Michael LaCour, Sub-Investigator, UT Research Assistant Professor, Biomedical 
Engineering 
 Dr. Douglas Dennis, Co-PI, Colorado Joint Replacement, Orthopaedic Surgeon 
 Dr. Jason Jennings, Sub-Investigator, Colorado Joint Replacement, Orthopaedic Surgeon 
 Jacob Elkins, Sub-Investigator, Colorado Joint Replacement, Orthopaedic Surgeon 
 Lindsay Kleeman-Forsthuber, Sub-Investigator, Colorado Joint Replacement, 
Orthopaedic Surgeon 
 Clinical Research Staff, including Ms. Roseann Johnson, Ms. Anna Brady and Ms. Aviva 
Pollet, Colorado Joint Replacement 
 Radiation technician(s) will operate the fluoroscopy machine, Porter Adventist Hospital 
 Required MD present during the fluoroscopy procedure 
 Rebecca Robertson, Research Coordinator, UT staff 
 Researchers present during data collection at the University of Tennessee and/or the lead 
researchers appointed by Dr. Komistek. 
 Graduate students: 
 Garett Dessinger 
 Jarrod Nachtrab 
 Milad Khasian 
 Lauren Smith 
 Seth Coomer 
 * Undergraduate student researchers employed by CMR will be involved in 
analyzing the data after it has been collected and transferred to CMR’s digital 
data collection. Since subject information will be removed and replaced with the 
assigned identifiers before the data is transferred to the database, it will not be 
possible for these undergraduate students to be able to identify subjects. They 
will only have access to the study data that has been uploaded onto the secure 
CMR digital collection. These undergraduate student researchers will not have 
contact with subjects. 
 Institutional Review Boards 
 The University of Tennessee will/has waived oversight to WIRB. Reliance 
Agreement included. 
 Centura Health/Catholic Health Initiatives will/ has waived oversight to WIRB. 
Reliance Agreement included. 
 Western Institutional Review Board. 
 A representative from Breg, Inc. will be present at data collection to fit subjects with the 
brace properly. This individual will sign a pledge of confidentiality. 
 A representative from JointVue will be present at data collection to acquire 3 
dimensional bone images using JointVue’s ultrasound procedure and software. This 
individual will sign a pledge of confidentiality. 
 
Clinical Observations: 
There are no clinical observations made during this data collection or from the images obtained 
through data collection. UT researchers do not require any kind of report from the radiology 

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department. Unless the data collection site requires such a report, there will be no radiology 
report generated for this procedure conducted as a result of this study. Therefore, no RT will 
review such a report for the procedures, which would be the only way such a “significant 
problem” would be determined. No data will be returned to the physician’s office for evaluation 
or review. However, if researchers see anything in the imaging that is extremely out of the 
ordinary (e.g., floating body, severe dislocation, potential tumors [spots of incredibly dense tissue 
on bones and skin]), they will bring this to the attention of Drs. Dennis or Jennings or their staff.  
 
It is not anticipated that the imaging collected during this study would potentially provide benefit 
to specific subjects by influencing the physician’s treatment plan. 
 
BENEFITS 
The potential benefits from this study include, but are not limited to: 
 Better understanding of the joints analyzed with the same technique in the past. 
 Future brace design improvements based on the kinematic findings. 
 There is no intention of any direct benefit to participants of the study. Information related 
to the data gathered may be provided to Drs. Dennis or Jennings by the researchers if 
something out of the ordinary is seen during the imaging. However, researchers are not 
radiologists and cannot interpret anything they may see. If there is something within the 
imaging that is obviously wrong as mentioned above, then this could result in potential 
modification of a subject’s treatment plan if images collected as a result of this study 
reveal any kind of “significant problem.” 
 
COMPENSATION 
The participants in this study will receive a $50 onetime payment in the form of a check for participation 
that will be mailed to the participate after completion of their CT Scan. 
 
METHODS TO OBTAIN "INFORMED CONSENT" FROM PARTICIPANTS 
Informed consent will be obtained prior to any procedures being conducted. Subjects who are 
agreeable to participate will be scheduled to visit Porter Adventist Hospital on the day that UT 
researchers will travel there for data collection. Appointed staff from Colorado Joint 
Replacement and/or UT researchers will be responsible for consenting the participants, giving 
them ample time to review and complete the forms and assist the participants with review of the 
documentation, if the participants are unable to read the form on their own. Only upon signed 
consent will the subject be allowed to participate in the study. If the subject chooses to be 
removed from the study after participating, his/her video, fluoroscopy footage and ultrasound 
data that was collected will be managed according to the subject’s response on the Revocation of 
Consent form. A copy of his/her Revocation of Consent will be attached to his/her IC and placed 
in a separate, secure file for IRB review. These consent forms will be stored at UT, Knoxville 
and will be accessible by only the aforementioned personnel. 
 
Drs. Dennis and Jennings will not be present during the consenting process to avoid possible 
subject coercion to participate. Subjects may contact Colorado Joint Replacement with any 
questions they may have. 
 
From previous studies, we have determined that it takes approximately 15 minutes to consent a 
subject and answer any questions that s/he may have. We have also estimated approximately 20 
minutes for researchers to guide the subject through the steps of the procedure, allow the subject 

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to practice the activity and then to actually perform the activity under fluoroscopic surveillance; 
actual radiation exposure will be up to, but not more than two minutes. The ultrasound portion of 
the data collection should take approximately 10 minutes. We have estimated a total time of 
approximately 45 minutes for each subject to be consented and complete the fluoroscopy and 
ultrasound procedures. 

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ATTACHMENT 1 
 
Verdun FR, Bochud F, Gundinchet F, Aroua A, Schnyder P, Meuli R. Quality Initiatives 
Radiation Risk: What You Should Know to Tell Your Patient 1. Radiographics 2008 Nov 
28(7):1807-16. 
 
 
 
 

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ATTACHMENT 2 
Mettler, et al. “Effective Doses in Radiology and Diagnostic Nuclear Medicine.” Radiology 
248.1 (2008): 254-263. http://radiology.rsna.org/content/248/1/254.full.pdf+html 
 

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ATTACHMENT 3 
 
 

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ATTACHMENT 4