Abobotulinumtoxin A for Chronic Exertional Compartment Syndrome

(CECS Trial)

Recruiting at 1 trial location

Overseen By Lavanya Veda, MS, CCRC

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Emory University

Must not be taking: Aminoglycosides, Neuromuscular blockers

Disqualifiers: Neuromuscular disease, Claudication, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 5 weeks

42 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking drugs that interfere with neuromuscular function, like certain antibiotics or muscle relaxants.

What data supports the effectiveness of the drug AbobotulinumtoxinA for treating Chronic Exertional Compartment Syndrome?

Research shows that injections of botulinum toxin A, similar to AbobotulinumtoxinA, have been effective in treating chronic exertional compartment syndrome, with 15 out of 16 patients experiencing positive results and one patient remaining pain-free 11 months after treatment. ^{1 2 3 4 5}

Is Abobotulinumtoxin A safe for humans?

Botulinum toxin A, which includes Abobotulinumtoxin A, has been used safely in humans for various conditions, such as spasticity, with no reported cases of compartment syndrome or major bleeding episodes in a study of 110 patients. ^{1 3 4 5 6}

How does the drug AbobotulinumtoxinA differ from other treatments for chronic exertional compartment syndrome?

AbobotulinumtoxinA offers a unique, non-surgical option for treating chronic exertional compartment syndrome by using injections to reduce muscle tone and alleviate pain, unlike the traditional surgical approach of fascial release. This drug has shown promise in providing long-term relief without the need for surgery, which is significant given the high recurrence rate of symptoms after surgical treatment. ^{1 3 4 7 8}

Research Team

Lee Kneer

Principal Investigator

Emory University

Eligibility Criteria

This trial is for adult runners aged 18-65 who have been diagnosed with Chronic Exertional Compartment Syndrome (CECS), a painful leg condition. They must meet specific diagnostic criteria with compartment pressure testing to participate.

Inclusion Criteria

Group providing normative values for SWE and needle manometry - ICP assessments

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abobotulinumtoxinA or placebo injections for the treatment of CECS

5 weeks

1 visit (in-person) for injection

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

3 visits (in-person) at baseline, 5 weeks, and 3 months

Extension

Participants may continue to be monitored for long-term outcomes

Long-term

Treatment Details

Interventions

• AbobotulinumtoxinA
• Placebo

Trial Overview The study tests AbobotulinumtoxinA, a potential non-surgical treatment for CECS, against a placebo. It also aims to develop a non-invasive diagnosis method using ultrasound shear wave elastography (SWE).

Participant Groups

Group I: Treatment Group Experimental Treatment 1 Intervention

AbobotulinumtoxinA

Group II: Control Group Placebo Group 1 Intervention

Normal Saline

AbobotulinumtoxinA is already approved in European Union, United States for the following indications:

Approved in European Union as Dysport for:

• Glabellar lines
• Cervical dystonia
• Spasticity in adults
• Upper and lower limb spasticity in adolescents and children aged 2 and older

Approved in United States as Dysport for:

• Glabellar lines
• Cervical dystonia
• Spasticity in adults
• Upper and lower limb spasticity in adolescents and children aged 2 and older

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Ipsen

Industry Sponsor

Trials

358

Recruited

74,600+

David Loew

Ipsen

Chief Executive Officer since 2020

BA in Business Administration and MBA from the University of St. Gallen, Switzerland

Sandra Silvestri

Ipsen

Chief Medical Officer since 2023

MD, PhD

Findings from Research

In a study of 16 patients with chronic exertional compartment syndrome (CECS), botulinum toxin A (BoNT-A) injections showed moderate initial efficacy, with 68.75% of patients reporting pain reduction, allowing some to resume triggering activities.

However, pain recurrence was common, particularly among those with partial initial improvement, with a median recurrence time of 2.25 months for partial responders and 5 months for complete responders, indicating that while BoNT-A can provide temporary relief, long-term effectiveness may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum Toxin A for Chronic Exertional Compartment Syndrome: A Retrospective Study of 16 Upper- and Lower-Limb Cases. Charvin, M., Orta, C., Davy, L., et al.[2022]

A 5-week massage treatment combined with stretching significantly increased the work output in dorsiflexion to pain onset for athletes with anterior chronic exertional compartment syndrome (CECS), indicating improved function.

However, the massage treatment did not significantly change the postexercise intracompartmental pressures, suggesting that while it may enhance performance, it does not directly affect the underlying pressure issues associated with CECS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of chronic exertional anterior compartment syndrome with massage: a pilot study. Blackman, PG., Simmons, LR., Crossley, KM.[2019]

Chronic exertional compartment syndrome is marked by pain during physical activity that goes away with rest, and is diagnosed primarily through measuring intramuscular pressure, although this method lacks standardization.

Treatment options include reducing physical activity or performing a fasciotomy, with some studies suggesting that endoscopically assisted fasciotomy may be effective, but more research is needed to clarify the condition's causes and long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Exertional compartment syndrome]. Lecocq, J., Isner-Horobeti, ME., Dupeyron, A., et al.[2016]

Intracompartmental injections of botulinum toxin A (BoNT-A) have shown promise as a non-surgical treatment for chronic exertional compartment syndrome (CECS), with a previous case series reporting effectiveness in 15 out of 16 patients.

In a specific case involving a U.S. military service member, BoNT-A treatment resulted in the patient being pain-free for 11 months, suggesting it could be a viable long-term alternative to the standard surgical fascial release, which has a high recurrence rate of symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum Toxin as a Novel Treatment for Chronic Exertional Compartment Syndrome in the U.S. Military. Hutto, WM., Schroeder, PB., Leggit, JC.[2020]

In a study of 81 patients who underwent fasciotomy for chronic exertional compartment syndrome, a history of psychiatric disorders was linked to worse postoperative pain and functional outcomes, indicating that mental health can significantly impact recovery.

Patients with psychiatric disorders who were not on medication experienced more severe pain and lower activity levels post-surgery, while those on psychiatric medication showed improved pain severity, suggesting that medication may help mitigate some negative effects of psychiatric conditions on recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychiatric Disorders Are Predictive of Worse Pain Severity and Functional Outcomes After Fasciotomy for Chronic Exertional Compartment Syndrome of the Leg. Bi, AS., Shankar, DS., Avendano, JP., et al.[2023]

In a study of 110 stroke patients receiving botulinum toxin injections for spasticity, no cases of compartment syndrome were reported, indicating a strong safety profile for this treatment.

The study reviewed 674 injection cycles, demonstrating that botulinum toxin injections (both onabotulinumtoxinA and incobotulinumtoxinA) can be safely administered without major bleeding episodes in patients on various anticoagulant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of botulinum toxin treatment for spasticity and bleeding complications in patients with thrombotic risk. Phadke, CP., Thanikachalam, V., Ismail, F., et al.[2019]

Chronic exertional compartment syndrome is a painful condition affecting athletes, characterized by symptoms like muscle tightness and weakness, with its exact cause still unknown.

Management options include conservative treatments like gait re-training and botulinum toxin injections, as well as various surgical approaches, highlighting the need for a tailored treatment plan based on individual cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic Exertional Compartment Syndrome in Athletes: An Overview of the Current Literature. Tarabishi, MM., Almigdad, A., Almonaie, S., et al.[2023]

In a study of five patients with symptomatic accessory soleus muscle (ASM), local injections of botulinum toxin type A (BTX-A) successfully relieved exercise-induced leg pain, allowing all patients to return to normal physical activities.

The treatment was well tolerated with no observed side effects or motor deficits, suggesting that BTX-A could be a safe and effective conservative option for managing ASM symptoms before considering surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of botulinum toxin type A in symptomatic accessory soleus muscle: first five cases. Isner-Horobeti, ME., Muff, G., Lonsdorfer-Wolf, E., et al.[2017]

References

1. United States pubmed.ncbi.nlm.nih.gov

Botulinum Toxin A for Chronic Exertional Compartment Syndrome: A Retrospective Study of 16 Upper- and Lower-Limb Cases. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment of chronic exertional anterior compartment syndrome with massage: a pilot study. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

[Exertional compartment syndrome]. [2016]

4. England pubmed.ncbi.nlm.nih.gov

Botulinum Toxin as a Novel Treatment for Chronic Exertional Compartment Syndrome in the U.S. Military. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Psychiatric Disorders Are Predictive of Worse Pain Severity and Functional Outcomes After Fasciotomy for Chronic Exertional Compartment Syndrome of the Leg. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Patterns of botulinum toxin treatment for spasticity and bleeding complications in patients with thrombotic risk. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Chronic Exertional Compartment Syndrome in Athletes: An Overview of the Current Literature. [2023]

8. Denmark pubmed.ncbi.nlm.nih.gov

Use of botulinum toxin type A in symptomatic accessory soleus muscle: first five cases. [2017]