Non-Surgical Treatments for Compartment Syndrome

No longer recruiting at 3 trial locations

Overseen By Teonette Velasco, DPT

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Walter Reed National Military Medical Center

Disqualifiers: Prior botulinum injection, Prior compartment release, Recent lower limb injury, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new, non-surgical treatments for Chronic Exertional Compartment Syndrome (CECS) in the lower leg, a condition that causes pain during activities like running. It compares the effects of gait retraining (changing how someone runs) combined with either botulinum toxin injections or saline injections. The goal is to determine if these methods can effectively reduce pain and improve function without surgery. Individuals who experience leg pain from running and have been diagnosed with CECS may be suitable for this trial. Participants must be active duty service members who struggle with running due to leg pain. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that botulinum toxin injections can help manage chronic exertional compartment syndrome (CECS) before surgery. Recent studies found that these injections effectively reduce symptoms like pain and improve blood flow. They are generally well-tolerated, with few serious side effects reported.

For gait retraining, both home-based and supervised methods have shown promise in reducing pain and improving running ability in people with CECS. In one study, all participants improved their ability to run without pain, and 70% ran without symptoms after treatment. This suggests that these methods are safe and effective for many people.

Overall, past research has demonstrated a good safety record for the treatments under study. However, individual experiences may vary, so discussing any concerns with a healthcare provider is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these non-surgical treatments for compartment syndrome because they offer innovative approaches that could potentially improve patient outcomes. Unlike traditional treatments that often require invasive surgery, these options focus on less invasive methods. Botulinum toxin injections aim to reduce muscle pressure and pain, offering a novel mechanism by targeting muscle relaxation. Additionally, gait retraining, both home-based and supervised, provides a non-invasive way to alter walking patterns, which can help alleviate symptoms. These approaches could provide effective alternatives for patients who want to avoid surgery and still find relief.

What evidence suggests that this trial's treatments could be effective for Chronic Exertional Compartment Syndrome?

Research has shown that botulinum toxin injections, one of the treatments in this trial, can help manage chronic exertional compartment syndrome (CECS). In one study, patients experienced moderate symptom relief without major side effects. Another promising method being tested in this trial is gait retraining, which involves changing the way individuals walk or run. Studies indicate that both home-based and supervised gait retraining, separate treatment arms in this trial, can reduce pain and improve running ability. Some patients even reported running without any pain after treatment. These non-surgical options might serve as alternatives to surgery, which can have varying success rates and recovery times. ^{1 2 6 7 8}

Who Is on the Research Team?

Jeffrey Leggit, MD

Principal Investigator

Uniformed Services University of the Health Sciences

Are You a Good Fit for This Trial?

This trial is for active duty service members who can't run 2 miles without leg pain, have trouble with physical training due to lower leg symptoms, and are fluent in English. They must be diagnosed with CECS of the anterior or lateral compartments but haven't had botulinum injections, compartment release surgery, recent limb injuries requiring medical intervention, gait retraining recently, or any allergies to botulinum toxin.

Inclusion Criteria

I experience pain in my lower leg that prevents me from running.

I have been diagnosed with CECS in my lower leg based on a physical exam and tests.

I cannot run 2 miles without feeling pain or other symptoms.

Exclusion Criteria

I have had a botulinum injection in my affected lower leg.

I had surgery to relieve pressure in my lower leg.

You are allergic to botulinum toxin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive non-surgical treatment options including gait retraining and botulinum toxin or saline injections

6 weeks

Multiple visits for injections and gait retraining sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Regular follow-up visits at 3, 6, 12, 24, and 36 months post-injection

What Are the Treatments Tested in This Trial?

Interventions

• Botulinum Toxin Injection
• Home Based Gait Retraining
• Saline Injection
• Supervised Gait Retraining

Trial Overview The study compares non-surgical treatments for CECS: saline injections versus botulinum toxin injections and home-based versus supervised gait retraining. The goal is to see which method best reduces pain during exertion over a follow-up period of at least two years across multiple sites.

How Is the Trial Designed?

Group I: Supervised Gait Retraining + Botulinum Toxin Injection Experimental Treatment 2 Interventions

Group II: Home Based Gait Retraining + Botulinum Toxin Injection Experimental Treatment 2 Interventions

Group III: Supervised Gait Retraining + Saline Injection Active Control 2 Interventions

Group IV: Home Based Gait Retraining + Saline Injection Active Control 2 Interventions

Who Is Running the Clinical Trial?

Walter Reed National Military Medical Center

Lead Sponsor

Trials

149

Recruited

33,800+

Uniformed Services University of the Health Sciences

Collaborator

Trials

130

Recruited

91,100+

Published Research Related to This Trial

A case study of a 36-year-old soldier with traumatic brain injury (TBI) showed that body weight-supported treadmill training (BWSTT) combined with goal-directed therapy improved his gait quality, speed, and distance ambulated.

The results suggest that BWSTT may be an effective intervention for improving mobility in TBI patients, but more research is needed to confirm its efficacy and suitability for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gait rehabilitation with body weight-supported treadmill training for a blast injury survivor with traumatic brain injury. Scherer, M.[2014]

A 19-year-old female with an incomplete C6 spinal cord injury showed significant improvements in walking speed, endurance, and gait quality after 28.5 weeks of body weight supported treadmill training (BWSTT) at a very low frequency of 1.16 days per week.

The study highlights that even infrequent BWSTT, when combined with conventional rehabilitation, can lead to meaningful gains in mobility for individuals with spinal cord injuries, suggesting potential for broader applications in rehabilitation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Body weight supported treadmill training at very low treatment frequency for a young adult with incomplete cervical spinal cord injury. Young, DL., Wallmann, HW., Poole, I., et al.[2009]

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 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]

Supervised exercise therapy (SET) significantly improves maximal walking distance (MWD) and pain-free walking distance (PFWD) in patients with intermittent claudication compared to home-based exercise therapy (HBET) and walking advice (WA), with increases of approximately 120 and 210 meters after three months, respectively.

SET shows better outcomes for self-reported functional impairment and some quality of life measures compared to WA, while HBET does not demonstrate significant improvements over WA, indicating that SET is the most effective exercise intervention for enhancing walking capacity in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supervised exercise therapy versus home-based exercise therapy versus walking advice for intermittent claudication. Hageman, D., Fokkenrood, HJ., Gommans, LN., et al.[2022]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10171030/

A 60-Year-Old Man with a 34-Year History of Chronic ... Recent studies show botulinum toxin injections can be effective for the initial management of chronic exertional compartment syndrome (CECS) prior to surgery.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05006417

Botox for the Treatment of Recurrent Chronic Exertional ... 10 participants with Recurrent Chronic Exertional Compartment Syndrome (R-CECS) will be enrolled in a 6 month study at the University of Wisconsin Hospitals ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05466539

Chronic Exertional Compartment Syndrome (CECS ... 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 ...

5. cureus.com cureus.com/articles/326100-outcomes-of-fasciotomy-versus-conservative-management-for-chronic-exertional-compartment-syndrome-a-systematic-review-and-meta-analysis

Outcomes of Fasciotomy Versus Conservative ... Studies comparing surgical and non-surgical approaches suggest that fasciotomy is more effective in alleviating pain and restoring activity ...

6. mirrorusuhs.org mirrorusuhs.org/mirror-projects/project5

Registry Development and Non-Surgical Treatment ... A newer proposed treatment is the intramuscular administration of onabotulinumtoxin A, also known as botulinum toxin A or BoNT-A into the muscles of the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7540008/

Systematic review of outcome parameters following treatment ... Intramuscular pressure before and after botulinum toxin in chronic exertional compartment syndrome of the leg: a preliminary study. Am J Sports Med. 2013;41 ...

8. journals.lww.com journals.lww.com/cjsportsmed/fulltext/2022/07000/chronic_exertional_compartment_syndrome_caused_by.4.aspx

Chronic Exertional Compartment Syndrome Caused by... Symptom reduction and normalization of venous flow after targeted botulinum toxin injections. Results: Baseline imaging demonstrated CECS and functional venous ...