Clinical trial NCT05466539: Chronic Exertional Compartment Syndrome (CECS) Treated With Abobotulinumtoxin A
Official title: Chronic Exertional Compartment Syndrome (CECS) Evaluated With Needle Manometry and Shear Wave Elastography, and Treated With Ultrasound-Guided AbobotulinumtoxinA
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Compartment Syndrome of Leg
Keywords: Runners
Lower extremity pain
Exertional Compartment Syndrome of the Leg
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Ipsen
First posted: 2022-07-20
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Chronic Exertional Compartment Syndrome (CECS) is a painful condition affecting runners and it is caused by a reversible increase in pressure within a closed compartment in the leg. Currently, to diagnose CECS, a large needle is placed into the muscle to measure pressure, which is invasive and painful. After diagnosis, the gold standard of treatment is surgery, which is also invasive, involves a prolonged return to play, and has a significant number of treatment failures. A growing literature has suggested alternative methods to both diagnosis and treatment that include the use of ultrasound to investigate muscle stiffness with shear wave elastography (SWE), and treatment with botulinum toxin injection into the muscle.

The investigators propose a single-site randomized clinical trial to investigate the use of abobotulinumtoxinA in the treatment of CECS. Researchers also look to develop a non-invasive method for the diagnosis of CECS using SWE. To the researchers' knowledge, this is the first randomized study investigating the medication to treat this cause.

The study will take place at Emory's outpatient sports medicine clinic. Potential participants will primarily be identified and recruited from the departments of Physical Medicine and Rehabilitation, Orthopedics, Physical Therapy, and Sports medicine as a part of regular clinical care. Participants will be included in the randomized portion of the study if they meet the previously established diagnostic criteria for CECS with compartmental pressure testing.

This would be a landmark study to provide evidence for the use of an abobotulinumtoxinA in the treatment of CECS, leading to the potential avoidance of a surgical procedure. It could also change the means of diagnosis without the use of painful and invasive needle pressure testing that would provide patients and athletes with ease of care.

Detailed description: Chronic exertional compartment syndrome (CECS) is an underdiagnosed condition and a cause of lower extremity pain often observed in running athletes. In runners, CECS is characterized by a reversible increase in pressure within an inelastic fascial compartment(s) of the lower extremity, leading to compromised tissue perfusion and subsequent pain and neurologic symptoms. It impacts both pediatric and adult populations. As currently diagnosed and treated, chronic exertional compartment syndrome presents unique challenges. Evaluation of CECS includes a thorough history and physical exam to rule out other causes of exertional leg pain, but the differential diagnosis must remain high on the list. Needle manometry, an invasive and painful procedure, is therefore used to confirm the diagnosis of CECS by measuring intra-compartmental pressure (ICP).

A growing literature, however, positions ultrasound shear wave elastography (SWE) as a viable and attractive alternative to ICP testing as it is both non-invasive and cost-effective. Earlier efforts demonstrated that muscle compartment "hardness" may accurately and noninvasively predict ICP. Building on these, SWE now provides direct measures of related mechanical properties of muscle and compartment, namely, "stiffness", thereby demonstrating promise as a diagnostic tool for CECS. Fasciotomy, currently the most well-accepted treatment approach, still has a significant number of treatment failures, demonstrating the need for additional options. A series of case reports have highlighted the potential merits of botulinum toxin as an alternative non-invasive treatment to surgery. Further, there is a growing consensus that desired BoNT targeting is best achieved through incorporating ultrasound guidance during the injection. The largest case series study to date reported that 15/16 patients with CECS had complete exertional pain relief with aboBoNTA. However, the apparent high dosing also led to a reduction in strength in 11/16 patients - An average of 288 units for the anterior compartment and 180 for the lateral compartment. In sum, the optimal dosage has yet to be determined.

Recently, the research team reported a case of a 39-year-old female runner presenting with lower extremity pain. CECS was confirmed with ICP. In addition, SWE was utilized in diagnosis and management. Briefly, SWE testing showed post-exercise increases in "stiffness" in the right Tibialis Anterior and left Fibularis Brevis relative to baseline measures. To provide perspective, both pre- and post-exercise SWE measures were elevated in this patient compared to two age and sex-matched controls. Following onaBoNTA treatment, further SWE measures revealed a reduction in patient muscle stiffness from the initial pre- and post-exercise treadmill testing, reaching levels comparable to the two asymptomatic age and sex-matched controls by week 6. Collectively, these results support a relationship between changes in intra-compartmental pressure as measured by needle manometry and muscle compartment "stiffness" as measured by SWE, and, as such, a role for SWE in CECS diagnosis and management.

In sum, SWE-based diagnosis coupled with ultrasound-enhanced injection accuracy are introduced to potentially complement and/or replace traditional approaches, which have challenged the diagnosis and management of CECS.

Eligibility criteria: Baseline Comparator Group:

Inclusion Criteria:

* Adult male and female runners aged 18-65 years
* Group providing normative values for SWE and needle manometry - ICP assessments

Exclusion Criteria:

* History of Neuromuscular disease, serious soft-tissue injury, fractures, and surgery to the lower limb(s).

Treatment Groups:

Inclusion Criteria:

* Confirmatory pressure values at diagnosis: Pre-exercise \> 15 mmHg; 1-min. post \> 30mmHg; or 5-min. post \> 20mmHg
* Ages 18-65 years inclusive at study onset.
* Ability to adhere to protocol.
* Botulinum toxin naïve (lower extremity). Others previously treated, \> than 6 mos. before study entry.

Exclusion Criteria:

* Diagnosis of comorbid pain conditions, including claudication and/or popliteal artery entrapment syndrome.
* Serious soft tissue injury, fractures, or surgery in the lower limb(s) \< than 12 months before study entry.
* Current need for surgery at any level of the lower extremity.
* Treatment with any drug known to interfere with neuromuscular function (e.g., aminoglycoside antibiotics or neuromuscular blocking agents).
* Any other medical condition, laboratory, or diagnostic procedure finding that might preclude the administration of aboBoNTA (Dysport®).
* Ongoing infection at the injection sites.
* Diagnosed as either resistant or sensitive to botulinum toxin treatment of any type or to any components of Dysport®
* Cow milk protein allergy.
* Vulnerable patient populations such as adults unable to consent, pregnant women, prisoners, persons who have not obtained the legal age for consent to treatment or procedures

Primary outcomes:
measure: Absolute change from baseline in the Visual Analog Scale (VAS) at 3 months following treatment
timeFrame: Baseline and 3 months
Secondary outcomes:
measure: Absolute change from baseline in the Visual Analog Scale (VAS) at 5 weeks following treatment
timeFrame: Baseline and 5 weeks
measure: Absolute and Relative change from baseline in the Patient-Reported Outcomes from the University of Wisconsin Running Injury and Recovery Index (UWRI).
timeFrame: Baseline, 5 weeks and 3 months
measure: Absolute and Relative change from baseline in the Ultrasound shear wave elastography measure: stiffness in kilopascals (kPa)
timeFrame: Baseline, 5 weeks and 3 months
measure: Absolute and Relative change from baseline in the Ultrasound shear wave shear wave velocity (m/s) (SWE)
timeFrame: Baseline, 5 weeks and 3 months
measure: Absolute and Relative change from baseline in the Single Assessment Numerical Evaluation (SANE)
timeFrame: Baseline, 5 weeks and 3 months
measure: Absolute and Relative change from baseline in the Goal Attainment Scaling (GAS)
timeFrame: Baseline, 5 weeks and 3 months
measure: Absolute and Relative change from baseline in the Manual Muscle Testing (MMT)
timeFrame: Baseline, 5 weeks and 3 months
measure: Dynamometric Testing (DT) for both legs
timeFrame: Baseline, 5 weeks and 3 months
measure: Absolute and Relative change from baseline in the Ankle Range of Motion (Ankle ROM) using a goniometer
timeFrame: Baseline, 5 weeks and 3 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Sports Medicine-Dunwoody
state: Georgia
city: Brookhaven
country: United States
facility: Emory Hawks Sports Medicine Center
state: Georgia
Study officials:
affiliation: Emory University
name: Lee Kneer
role: PRINCIPAL_INVESTIGATOR
References: