Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05247541 |
| Other study ID # |
CG20003 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2/Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2020 |
| Est. completion date |
December 1, 2023 |
Study information
| Verified date |
December 2023 |
| Source |
Thomas Jefferson University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Chronic exertional compartment syndrome (CECS) is an innocuous condition seen primarily in
10-60% of young active people with exercise induced leg pain. With an average delay in
diagnosis of 2 years, early identification is crucial as delays have led to poor surgical
outcomes after fasciotomy. Diagnosis is currently made by compartment pressure (CP) testing,
which is invasive, painful and demonstrates variable accuracy. There is no literature on the
role of shear wave elastography (SWE) and/or subharmonic assisted pressure estimation (SHAPE)
with microbubbles in diagnosing CECS. Ultrasound contrast agents are FDA-approved and are
extremely safe. In this single-blinded prospective pilot study, the accuracy of SHAPE and SWE
will be evaluated and compared to the current gold standard of compartment testing in
patients with suspected CECS. Muscle stiffness and record a quantitative assessment of
enhancement and hydrostatic pressures will be documented and correlated with compartment
testing results based on a reference standard modified Pedowitz criteria for CECS
Description:
Chronic exertional compartment syndrome (CECS) is an innocuous condition seen primarily in
10-60% of young, active people with exercise induced leg pain. Patients present with anterior
lower extremity pain that worsens with exercise and resolves after rest. CECS arises from
increased intra-compartmental pressure causing impaired tissue perfusion. The average delay
in diagnosis and subsequent treatment is 2 years, which has been shown to decrease the
success rate of both conservative and surgical therapy. Definitive treatment is with
fasciotomy, which has a success rate of up to 95%.
The etiology of CECS is not well understood but is thought to arise from volume expansion of
a muscle within a noncompliant space bounded by fascia and bone resulting in insufficient
blood flow and a resultant oxygen supply and demand mismatch in that compartment. In some
cases the physiological response may lead to a 20% increase in muscle volume. Several risk
factors have been identified including pre- existing fascial defects (seen in 40% of CECS
patients) and a smaller capillary density to muscle size ratio. In rare cases, CECS may
progress to acute compartment syndrome - a surgical emergency requiring emergent fasciotomy.
The gold standard for diagnosing CECS is direct measurement of intra-compartmental pressures
with maximum sensitivity and specificity in recent studies of 93% and 74%. However, in rare
circumstances, diagnosis can be made on clinical basis alone. Compartment pressure testing is
performed by inserting a handheld large gauge needle with a pressure monitor into the muscle
and measuring the compartment pressure directly (in mmHg). Direct compartment testing is
invasive, painful, and carries a complication risk of neurovascular damage and infection.
Furthermore, there is significant variability in this technique with some studies finding
more than >5 mmHg difference in 40% of compartmental pressure measurements.
In the diagnostic algorithm of CECS, imaging is primarily used to rule out other more common
causes of lower extremity leg pain such as medial tibial stress syndrome (MTSS), stress
fractures, and muscle strains. Several non-invasive imaging modalities have been used to
diagnose CECS. When compared to pressure testing, MRI showed similar sensitivity, but lower
specificity (< 60%). While MRI has shown some diagnostic promise, it is more expensive, less
ubiquitous, and less accurate than compartment testing. Near-infrared spectroscopy, which
measures hemoglobin O2 saturation of tissues, has shown to have clinically equivalent
sensitivies (85%) compared to compartment testing, however, it is not readily available.
A clinical exam alone is insensitive and non-specific in the diagnosis of CECS. Therefore,
surgeons must rely on a combination of clinical exam and imaging to determine whether a
patient is a surgical candidate. An accurate, non-invasive, and cost effective diagnostic
tool does not currently exist for patients with suspected CECS. SWE is a safe, non-invasive
and relatively inexpensive modality that has wide ranging diagnostic capabilities. SWE is
used measure liver stiffness thereby staging fibrosis in chronic liver disease, following up
previously diagnosed hepatic fibrosis and evaluating patients with portal hypertension.
Recently, the utility of SWE in musculoskeletal imaging has increased; for example SWE is
currently being using to evaluate tendinopahic achilles tendons with some clinical success.
FDA-approved ultrasound contrast agents are safe, non-nephrotoxic, non-hepatotoxic contrast
agents that act as echo-enhancers before dissipation from the intravascular space. SHAPE
utilizing microbubbles has been used for the noninvasive estimation of hydrostatic blood
pressure to monitor interstitial fluid pressure in tumors, assess the degree of portal
hypertension, and to monitor neoadjuvant chemotherapy for breast cancer patients. However, no
series studies exist characterizing SHAPE and SWE for the screening or diagnosis of CECS.
This study will assess whether SHAPE and/or SWE can accurately detect increased
intra-compartmental pressures when compared to the reference standard of intra-compartmental
pressure testing.
This study will be performed as a prospective single-blinded pilot study of patients with
suspected CECS who is eligible to participate in the study and meets inclusion and exclusion
criteria (described below). A research Coordinator will meet with the patient to explain the
study in full. If the prospective subject expresses interest in participating in the study an
investigator will approach the patient to obtain consent. All sonographic research portions
of the study will be performed by a certified and experienced sonographer. The compartment
testing portion of the study will be performed as part of the subjects standard of care.
Pre-exercise SWE: After determining inclusion, patients will undergo pre-exercise SWE using a
Logiq E10 ultrasound system (GE Healthcare, Waukesha WI) with a linear array transducer. All
images will be obtained with the ankle in a neutral position. Conventional B-mode imaging
will be used to identify the muscle of interest. Imaging will be used to guide placement of
ROIs, which can be adjusted by the operator After shear waves have propagated through the
muscle of concern tissue displacement maps are used to calculate shear-wave velocity in
meters per second. Elasticity parameters, including mean (Emean), maximum (Emax), minimum
(Emin), and standard deviation (ESD) will be displayed on the ultrasound machine monitor.
Tissue stiffness will then be directly calculated, expressed as the shear modulus G in
kilopascals (kPa). Quantitative shear modulus maps will be generated.
Pre-exercise SHAPE: The modified software allowing the E10 to operate in subharmonic imaging
(SHI) mode will permit acquisition of subharmonic data. All images will be obtained with the
ankle in the neutral position. An 18-24 gauge intravenous line will be placed in either the
right or left Upper extremity. The contrast will be an intravenous infusion of 2 vials of
Definity (Lantheus Medical Imaging, N Billerica, MA) in 50 mL of saline infused over 5-10
minutes. The route of administration and dosages follow the recommendations issued by the
manufacturer. SHI will be performed using the same scanner. A broad bandwidth C2-9 convex
probe will be used to acquire conventional and subharmonic images (transmitting at 5.8 MHz
receiving at 2.9 MHz). The investigators will run a power optimization algorithm to establish
individual acoustic parameters settings for the case (initial imaging study only). After
power optimization, the Region of Interest (ROI) will be enlarged to collect data from the
compartment of interest over 5 seconds and findings are averaged after processing. Both the
fundamental data (B-mode data at 4 MHz) and the SHI data will be analyzed offline.
Exercise protocol: Patients will perform common exercise that causes symptoms is
walking/running using a standardized exercise treadmill protocol: 3.7 mph against a 5° slope
for 6 minutes or until symptom onset. If symptoms do not occur by 6 minutes of exercise,
speed will be increased to a maximum of 5 mph and/or slope will be increased to 8° for an
additional 6 minutes or until symptom onset. If the patient is still asymptomatic, he or she
will exercise for another 4 minutes at 5 mph and an 8° slope or until symptom onset.
Immediate post-exercise SWE and SHAPE will be performed using the same optimization
parameters and protocol established for the pre-exercise portion of the study. Patients will
be assigned a dummy code and de-identified SWE and SHI data will be stored for off line
analysis.
The entire ultrasound portion of the study will last under 60 minutes and will be performed
while the patient is under constant observation. The patient's vital signs will be monitored
through the entire examination with frequent monitoring by the physician present. Active
patient participation will conclude on completion of the study protocol.
