Non-Surgical Treatments for Compartment Syndrome

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

46 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates non-surgical treatments like gait retraining and botulinum toxin injections for highly active individuals with lower leg pain due to CECS. These treatments aim to reduce pain by changing movement patterns and relaxing muscles. Botulinum toxin injections have been used to treat spasticity in stroke patients and muscle imbalance syndromes in sports medicine.

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 botulinum toxin injection generally safe for humans?

Botulinum toxin injections have been used safely for various conditions, including spasticity in cerebral palsy and chronic exertional compartment syndrome, with some reports of mild adverse events. In a study of patients with cerebral palsy, 4% experienced severe adverse events, but overall, the treatment is considered to have a satisfactory safety profile. ^{1 2 3 4 5}

How is the treatment for compartment syndrome different from other treatments?

This treatment for compartment syndrome is unique because it combines Botulinum Toxin Injection, which is a drug that relaxes muscles, with gait retraining exercises that can be done at home or under supervision. This approach is different from traditional surgical options and focuses on improving walking ability and muscle function without surgery. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment for compartment syndrome?

Research shows that botulinum toxin injections and gait retraining can be effective for treating chronic exertional compartment syndrome (CECS). Botulinum toxin has been used successfully in some cases, and changing running or marching techniques has shown promising results in improving symptoms. ^{4 11 12 13 14}

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

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]

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]

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]

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]

Citations

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

Nonoperative Management of Chronic Exertional Compartment Syndrome: A Systematic Review. [2022]

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

The Effectiveness of a 6-Week Intervention Program Aimed at Modifying Running Style in Patients With Chronic Exertional Compartment Syndrome: Results From a Series of Case Studies. [2022]

4. Denmark pubmed.ncbi.nlm.nih.gov

Systematic review of outcome parameters following treatment of chronic exertional compartment syndrome in the lower leg. [2021]

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

MODIFYING MARCHING TECHNIQUE IN MILITARY SERVICE MEMBERS WITH CHRONIC EXERTIONAL COMPARTMENT SYNDROME: A CASE SERIES. [2022]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Questionnaire about the adverse events and side effects following botulinum toxin A treatment in patients with cerebral palsy. [2018]

8. England pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

Botulinum toxin treatment of spasticity in diplegic cerebral palsy: a randomized, double-blind, placebo-controlled, dose-ranging study. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Supervised exercise therapy versus home-based exercise therapy versus walking advice for intermittent claudication. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Exercise training for intermittent claudication: a narrative review and summary of guidelines for practitioners. [2023]

12. Netherlands 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. [2009]

13. England pubmed.ncbi.nlm.nih.gov

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

14. France pubmed.ncbi.nlm.nih.gov

[The treatment of intermittent claudication by physical retraining of the non-hospitalised patient. Evaluation of effectiveness in a group of 40 patients (author's transl)]. [2007]