Abobotulinumtoxin A for Chronic Exertional Compartment Syndrome

(CECS Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks a less invasive method to diagnose and treat Chronic Exertional Compartment Syndrome (CECS), a painful condition often affecting runners. Researchers are testing abobotulinumtoxinA, commonly known as botulinum toxin, as a potential treatment to avoid surgery and speed up recovery. They are also exploring a new, painless diagnostic method for CECS using ultrasound technology. Runners already diagnosed with CECS through current pressure tests might be suitable candidates for this study. As a Phase 4 trial, the treatment has FDA approval and proven effectiveness, offering participants the chance to benefit from established therapies while contributing to broader understanding.

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 is the safety track record for abobotulinumtoxinA?

Research has shown that abobotulinumtoxinA, a type of botulinum toxin, is generally safe and well-tolerated. In one study, 110 stroke patients received these injections to treat muscle stiffness, and no cases of compartment syndrome, a serious condition, were reported. This suggests the treatment usually doesn't cause serious problems. Additionally, another study found that these injections reduced muscle pressure and pain in patients with chronic exertional compartment syndrome (CECS) for up to nine months, demonstrating positive results without major safety issues.

While abobotulinumtoxinA is being tested for CECS in this study, the FDA has already approved it for other uses, which adds to its safety reassurance. However, always discuss any concerns with a healthcare provider before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike standard treatments for Chronic Exertional Compartment Syndrome, which often involve physical therapy or surgery, AbobotulinumtoxinA offers a novel approach by using a neurotoxin to reduce muscle pressure and pain. This treatment works by temporarily blocking nerve signals to the muscles, which can help alleviate the symptoms more effectively and with less invasiveness than surgery. Researchers are excited about its potential to provide relief with fewer side effects and quicker recovery times compared to traditional surgical procedures. This innovative mechanism of action could represent a significant advancement in managing this condition.

What evidence suggests that abobotulinumtoxinA might be an effective treatment for chronic exertional compartment syndrome?

Research has shown that abobotulinumtoxinA may help treat Chronic Exertional Compartment Syndrome (CECS). In earlier studies, people with CECS who received BoNT-A injections experienced moderate improvements without major side effects. Another study found reduced muscle stiffness, a main symptom of CECS, after treatment. While these results are promising, this trial continues to study abobotulinumtoxinA as an alternative to surgery for CECS. Participants will receive either abobotulinumtoxinA or a placebo, potentially offering a less invasive treatment option for this painful condition. ^{1 2 6 7 8}

Who Is on the Research Team?

Lee Kneer

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34282061/

A Retrospective Study of 16 Upper- and Lower-Limb Cases In 16 individuals with CECS treated with BoNT-A injections, we observed moderate efficacy without major adverse effects, but an initial improvement was often ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05466539

Chronic Exertional Compartment Syndrome (CECS ... Following onaBoNTA treatment, further SWE measures revealed a reduction in patient muscle stiffness from the initial pre- and post-exercise treadmill testing, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8666157/

Botulinum Toxin A for Chronic Exertional Compartment ... This case presentation offers supportive evidence that shear wave elastography may provide an alternative method of diagnosis of chronic exertional compartment ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05466539/chronic-exertional-compartment-syndrome-cecs-treated-with-abobotulinumtoxin-a

Chronic Exertional Compartment Syndrome (CECS) ... The investigators propose a single-site randomized clinical trial to investigate the use of abobotulinumtoxinA in the treatment of CECS.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03339921?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(%22Chronic%20Exertional%20Compartment%20Syndrome%22))))&rank=5

Botulinum for Chronic Exertional Compartment Syndrome An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

6. withpower.com withpower.com/trial/phase-4-compartment-syndromes-7-2022-3cd6c

Abobotulinumtoxin A for Chronic Exertional Compartment ... In a study of 110 stroke patients receiving botulinum toxin injections for spasticity, no cases of compartment syndrome were reported, indicating a strong ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23969633/

Intramuscular pressure before and after botulinum toxin in ... In this case series, BoNT-A reduced the IMP and eliminated exertional pain in anterior or anterolateral CECS of the leg for up to 9 months ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03339921

Botulinum for Chronic Exertional Compartment Syndrome Clinical data that will be analyzed for research purposes in both groups include age, sex, height, weight, body mass index, time to diagnosis, minutes of ...