The goal of this study is to characterize redox homeostasis in post-traumatic
osteoarthritis (PTOA), with the goal of examining the impact of extracorporeal shockwave
therapy (ESWT). We will explore the following aims:
Specific Aim 1: Investigate the effects of ESWT treatment on participant-reported
functional outcomes and quality of life in individuals with PTOA of the knee. We
hypothesize that those in ESWT group will report greater improvements in pain level,
function and quality of life compared to those individuals in the sham group.
Specific Aim 2: Determine if ESWT influences gait biomechanics of participants with PTOA.
We hypothesize that those in ESWT group will display biomechanics during gait that more
closely resemble the biomechanics of a healthy individual. We anticipate that this aim
will identify if a more favorable inflammation burden will reduce abnormal biomechanics,
or if further interventions will be necessary.
Specific Aim 3: Investigate the influence of ESWT on joint conductivity and inflammation
of the knee using bioimpedance spectroscopy (BIS). This has yet to be explored in the
PTOA population and thus our objective is to explore knee-site tissue changes in PTOA
following ESWT. Thermal pattern has been used to identify active inflammation in the
osteoarthritic knee with respect to a healthy knee. We hypothesize that there will be
improvements in tissue changes and thermal pattern in the knee measured by BIS and
thermal camera following ESWT.
Specific Aim 4: Evaluate baseline values of knee range of motion, lower extremity
strength, and bone health and determine if ESWT may influence these measures. We will
collect measures of knee range of motion, quadriceps isometric strength and rate of
torque development with handheld dynamometry, and measurements of bone density with DXA
scans. We hypothesize that knee range of motion, quadriceps strength and rate of torque
development will yield greater improvements following ESWT compared to sham treatment.
Specific Aim 5: Assess the influence of ESWT on chronic pain. We will investigate if ESWT
will reduce chronic pain in participants with knee OA, thus resulting in improved
functional outcomes. We hypothesize that individuals will have reduced levels of PPT and
improved scores on PainDETECT following ESWT compared to sham treatment.
Specific Aim 6: Evaluate the effects of ESWT on bone turnover and joint integrity. We
hypothesize that those in ESWT group will demonstrate more favorable joint integrity
compared to individuals in the sham group.
Specific Aim 7: Investigate the effects of ESWT treatment on redox and inflammatory
biomarkers. We hypothesize that redox and inflammatory biomarkers will increase above
pre-treatment values following ESWT treatment and that ESWT will provoke a greater
biomarker response than sham treatment. Finally, upon resolution of this acute response,
we hypothesize that biomarker values assessed after treatment completion will reveal
favorable redox balance and inflammation burden relative to pre-treatment values and be
associated with improvement in functional measures of knee function.
This is a prospective, placebo control randomized control trial with an elective
cross-over design that aims to understand influence of ESWT in the management of PTOA
after ACL reconstruction. Participants involvement will last 4-8 months depending on
participant allocation and whether they elect to participate in cross-over portion of
study. Each participant will complete biomechanical assessment of gait using instrumented
treadmill while wearing motion capture markers, accelerometers and EMGs, have thermal
images and bioimpedance measures collected, have their height and leg length measured,
complete measures of knee range of motion and quadriceps strength. To document presence
and degree of PTOA, each participant will complete weight-bearing (WB) X-rays of both
knees, an MRI of involved knee, and complete bone density scans (DEXA). Blood and serum
biomarkers of inflammation and candidate markers of joint injury and healing will be
recorded. Each participant will complete functional outcomes before and after treatment.
To ensure standard exercise program is completed per standard of care, each participant
will be instructed on a home exercise program to complete during the study. During the
treatment session, participants will receive either ESWT or sham ESWT with measures of
oxidative stress obtained. At baseline, treatment session 3, 8-weeks and 4-months,
participants will complete patient reported outcome measures (PROMs). At the 4-month time
point after starting ESWT, participants will repeat the following measures: PROMs,
biomechanical assessment with surface EMG, thermal images, bioimpedance, knee range of
motion, quadriceps strength, quantitative sensory testing (QST), MRI of injured knee, and
venous and fingerstick blood draws. For those participants who were randomized to the
sham ESWT group, they will have the option to cross-over at 4 months and receive ESWT.
Study Procedures:
Participants will be randomized into ESWT treatment group or sham ESWT control group
using a block randomization generator that is implemented into REDCap. Based on
anticipated 20% attrition, our goal is to assign 35 participants to each group.
Control Group: Sham ESWT Arm:
All participants will review the exercise program prior to randomization and receiving
sham ESWT treatment. The standard operating procedures for ESWT will be followed and will
include review of procedure protocol and post-procedure care. Participants will come into
the office for three treatment visits. After collecting baseline variables and after
blood is drawn, they will receive sham ESWT using the OrthoPlus Ultra 100/radial D-Actor
and Duolith SD1 T-Top focused shockwave devices. The device will be placed on the same
landmarks as that of the ESWT treatment group; however, no shockwaves will be
administered; rather, an audio recording that mimics the sound of shockwave will be
played. A curtain will obscure participants from viewing their knee and the device to
blind them from treatment they are receiving.
Treatment Group: ESWT Arm:
All participants will review the exercise program prior to randomization and receiving
treatment. Participants in the ESWT group will receive ESWT. The standard operating
procedures for ESWT will be followed and will include review of procedure protocol and
post-procedure care. Participants will come into the office for three treatment visits.
After collecting baseline variables and after blood is drawn, they will receive ESWT
using the OrthoPlus Ultra 100/radial D-Actor and Duolith SD1 T-top focus. Radial pressure
waves will be applied using the Extracorporeal Pressure Activation Treatment (EPAT)
device. For the anterior knee, patella tendon, vastus lateralis, and vastus medialis,
treatment will aim for 1500 strikes at induction dose of 1.5 bars and titrating up by 0.5
bars to 3 bars and this will be performed to participant tolerance to pain, as pain is
experienced due to clinical focusing technique which is standard of care in delivering
effective treatment. Half of treatment (1500 strikes) will be delivered to the patellar
tendon and 1500 strikes to the quadricep tendon and distal quadricep muscles with the
patient in supine position with knee flexed during treatment to patellar tendon and knee
in extension to treat the quadricep region. For the calf muscles, the patient will be
positioned prone and a similar protocol of starting at 1.5 and titrating up as tolerated
to 3 bars will be administered and this will also be performed to participant tolerance.
With the patient in supine position with knee bent, anatomical landmarks of tibial
plateau and femoral condyle will be identified. Focused shockwave therapy will be applied
for 1000 shocks to four anatomical locations for a total of 4000 shocks. Each site will
receive 1000 shocks: medial and lateral tibial plateau and medial and lateral femoral
condyle. At each location, the patient will receive a lower energy setting of 200 shocks
to 0.05 MJ, then 200 at .10 MJ, 200 at 0.12 MJ and, 200 AT 0.15 MJ, and finally 200 at
.20 MJ to improve patient comfort to higher energy settings. These energy settings are
consistent with mild to moderate ESWT which are commonly used in clinical practice to
treat knee OA. During the ESWT treatment, a curtain will obscure participants from
viewing their leg to blind them from treatment they are receiving. Standard protocol for
the ESWT procedure will be followed, including safety assessment and monitoring.
Additionally, the patient will be prescribed a post-ESWT exercise protocol that is part
of the standard of care, which will be reviewed prior to first treatment and before
treatment allocation.
Visit Details:
Participants will come in for a total of seven to eight in-person visits during the
study, which will depend on if baseline visits are completed over two or three sessions
based on convenience for participants. For those participants who elect to participate in
cross-over at 4 months, they will complete up to 12 visits. Participant reported outcomes
will be collected using online survey through REDCap at 8-weeks (8 weeks is based on
initial time of ESWT or sham ESWT). The baseline visit will be a pre-trial assessment to
obtain baseline values for each patient. During the baseline visits, participants will
run on an instrumented treadmill with motion capture markers, accelerometers, and surface
EMG. Participants will have knee inflammation information recorded using thermal imaging
and tissue electrical characteristics using bioimpedance measures, have their heigh and
leg length measured, have their knee range of motion and strength measured, perform
quantitative sensory testing (QST), have an assessment of bone health and body
composition with a DEXA scan, have standard AP and lateral, as well as WB X-rays taken of
their knees, complete surveys regarding pain and function of the affected joint, and have
blood drawn to measure blood and serum biomarkers and obtain an MRI of participants'
arthritic knee.
After the pre-trial assessment participants will come in for one treatment session. A
post- treatment exercise protocol will be reviewed with all participants prior to
randomization. During the treatment session participants will be given ESWT or sham ESWT
depending on what treatment group they are randomized to. Blood will also be drawn to
analyze biomarkers. Participants will attend two additional treatment sessions. Blood
draw and finger stick will be performed prior to each treatment session. Participants
will complete questionnaires at the third treatment session and will be sent
questionnaires electronically through REDCap to be completed at 8 weeks follow-up.
Participants will return at 4 months for repeat MRI, thermal imaging, bioimpedance, knee
ROM, quadriceps strength and torque measures, QST, biomechanical assessment with surface
EMG, and will complete final questionnaires. At 4 months, participants in the sham ESWT
treatment group will have the option to elect to cross-over and receive three ESWT
treatments.
