Comparison of Non-Surgical Treatment Options for Chronic Exertional Compartment Syndrome (CECS)

Chronic Exertional Compartment Syndrome (CECS) in the lower leg is a debilitating condition in highly active individuals. Pain occurs in 1 or several leg compartments upon an exertional activity, typically running, that quickly dissipates once the activity stopped. Surgical fasciotomy is the standard for treating lower leg CECS, but success is variable. Complications may occur post-surgery and there is a potential for a repeat procedure. Recovery times post-surgery also vary greatly. Conservative treatments, such as gait retraining and botulinum toxin injections, are emerging as non-surgical options for the treatment of CECS with success through published case reports and case series. This study aims to evaluate the use of these non-surgical treatment options for CECS in the anterior and lateral leg compartments with a follow up for at least 2 years across multiple study sites.

Study Overview

• Status: Completed
• Conditions: Chronic Exertional Compartment Syndrome
• Intervention / Treatment: Behavioral: Home Based Gait Retraining; Drug: Saline Injection; Drug: Botulinum Toxin Injection; Behavioral: Supervised Gait Retraining

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20307
      • Walter Reed National Military Medical Center
  • North Carolina
    • Fort Bragg, North Carolina, United States, 28310
      • Womack Army Medical Center
  • Texas
    • Killeen, Texas, United States, 76544
      • Carl R. Darnell Army Medical Center
  • Virginia
    • Fort Belvoir, Virginia, United States, 22060
      • Fort Belvoir Community Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Active duty service
• Fluent in speaking and reading English
• Unable to run 2 miles without producing pain and/or symptoms
• Difficulty completing the running portion of their service-specific physical training due to pain and/or symptoms in their lower leg
• Meets clinical diagnostic criteria for CECS of the anterior or lateral compartment per clinical examination (palpation, intramuscular compartment pressure, lower leg MRI).

Exclusion Criteria:

• Prior botulinum injection in the lower leg compartment of the affected limb
• Prior compartment release of affected lower leg
• Recent (within the last 6 months) lower limb injury that needed medical intervention
• Completed formal gait retraining within the last 6 months
• Allergic to botulinum toxin
• Pregnant or breastfeeding
• Medical examination that indicates a condition other than CECS

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Home Based Gait Retraining + Saline Injection	Behavioral: Home Based Gait Retraining; The participants allocated to this group will have 1 session in the clinic with a trained medical professional and be given a gait retraining program to complete at home.; Drug: Saline Injection; The participant will receive a saline injection to their painful lower leg compartment(s).
Experimental: Home Based Gait Retraining + Botulinum Toxin Injection	Behavioral: Home Based Gait Retraining; The participants allocated to this group will have 1 session in the clinic with a trained medical professional and be given a gait retraining program to complete at home.; Drug: Botulinum Toxin Injection; The participant will receive a botulinum toxin injection to their painful lower leg compartment(s).
Active Comparator: Supervised Gait Retraining + Saline Injection	Drug: Saline Injection; The participant will receive a saline injection to their painful lower leg compartment(s).; Behavioral: Supervised Gait Retraining; The participants allocated to this group will attend 8 sessions during the course of 6 weeks in the clinic with a trained medical professional to complete a supervised gait retraining program.
Experimental: Supervised Gait Retraining + Botulinum Toxin Injection	Drug: Botulinum Toxin Injection; The participant will receive a botulinum toxin injection to their painful lower leg compartment(s).; Behavioral: Supervised Gait Retraining; The participants allocated to this group will attend 8 sessions during the course of 6 weeks in the clinic with a trained medical professional to complete a supervised gait retraining program.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
University of Wisconsin Running Injury and Recovery Index Score at Baseline	The UWRI is scored based on points assigned from self-reported evaluations of running capability. 9 questions are scored on a Likert Scale from 0 to 4, indicating ranges from incapable to optimal function, respectively. The total score can range from 0-36; higher scores indicates better running ability.	baseline
University of Wisconsin Running Injury and Recovery Index Score at 8 Weeks Post-Injection	The UWRI is scored based on points assigned from self-reported evaluations of running capability. 9 questions are scored on a Likert Scale from 0 to 4, indicating ranges from incapable to optimal function, respectively. The total score can range from 0-36; higher scores indicates better running ability.	8-week
University of Wisconsin Running Injury and Recovery Index Score at 3-months Post-injection	The UWRI is scored based on points assigned from self-reported evaluations of running capability. 9 questions are scored on a Likert Scale from 0 to 4, indicating ranges from incapable to optimal function, respectively. The total score can range from 0-36; higher scores indicates better running ability.	3-month
University of Wisconsin Running Injury and Recovery Index Score 6-months Post-injection	The UWRI is scored based on points assigned from self-reported evaluations of running capability. 9 questions are scored on a Likert Scale from 0 to 4, indicating ranges from incapable to optimal function, respectively. The total score can range from 0-36; higher scores indicate better running ability.	6-month
University of Wisconsin Running Injury and Recovery Index Score at 12-months Post-Injection	The UWRI is scored based on points assigned from self-reported evaluations of running capability. 9 questions are scored on a Likert Scale from 0 to 4, indicating ranges from incapable to optimal function, respectively. The total score can range from 0-36; higher scores indicate better running ability.	12-month
University of Wisconsin Running Injury and Recovery Index Score at 24-Months Post-Injection	The UWRI is scored based on points assigned from self-reported evaluations of running capability. 9 questions are scored on a Likert Scale from 0 to 4, indicating ranges from incapable to optimal function, respectively. The total score can range from 0-36; higher scores indicate better running ability.	24-month
Single Assessment Numerical Evaluation (SANE) Score at Baseline	A patient reported outcome measure consisting of 1 question that asks the individual to rate their current level of function on a scale from 0-100. A higher score suggests a higher level of function.	baseline
Single Assessment Numerical Evaluation (SANE) 8-weeks Post-Injection	A patient reported outcome measure consisting of 1 question that asks the individual to rate their current level of function on a scale from 0-100. A higher score suggests a higher level of function.	8-weeks
Single Assessment Numerical Evaluation (SANE) at 3-months Post-Injection	A patient reported outcome measure consisting of 1 question that asks the individual to rate their current level of function on a scale from 0-100. A higher score suggests a higher level of function.	3-months
Single Assessment Numerical Evaluation (SANE) at 6-months Post-Injection	A patient reported outcome measure consisting of 1 question that asks the individual to rate their current level of function on a scale from 0-100. A higher score suggests a higher level of function.	6-months
Single Assessment Numerical Evaluation (SANE) at 12-months Post-Injection	A patient reported outcome measure consisting of 1 question that asks the individual to rate their current level of function on a scale from 0-100. A higher score suggests a higher level of function.	12-months
Single Assessment Numerical Evaluation (SANE) at 24-months Post-Injection	A patient reported outcome measure consisting of 1 question that asks the individual to rate their current level of function on a scale from 0-100. A higher score suggests a higher level of function.	24-months
Global Rate of Change Score at 8-weeks Post-Injection	Global Rating of Change (GROC) is scored on a Likert Scale ranging from -7 to 7, indicating a range of self-perceived overall change in function at that time point compared to the baseline. Positive higher numbers indicate positive (improvement) and negative lower numbers indicate negative (decline). The participant chooses one number on the scale. Score ranges: (-) 7: A very great deal worse, (-) 6: A great deal worse, (-) 5: Quite a bit worse, (-) 4: Moderately worse, (-) 3: Somewhat worse, (-) 2: A little bit worse, (-) 1: A tiny bit worse (almost the same), (+) 1: A tiny bit better (almost the same), (+) 2: A little but better, (+) 3: Somewhat better, (+) 4: Moderately better, (+) 5: Quite a bit better, (+) 6: A great deal better, (+) 7: A very great deal better.	8-weeks
Global Rate of Change Score 3-months Post-Injection	Global Rating of Change (GROC) is scored on a Likert Scale ranging from -7 to 7, indicating a range of self-perceived overall change in function at that time point compared to the baseline. Positive higher numbers indicate positive (improvement) and negative lower numbers indicate negative (decline). The participant chooses one number on the scale. Score ranges: (-) 7: A very great deal worse, (-) 6: A great deal worse, (-) 5: Quite a bit worse, (-) 4: Moderately worse, (-) 3: Somewhat worse, (-) 2: A little bit worse, (-) 1: A tiny bit worse (almost the same), (+) 1: A tiny bit better (almost the same), (+) 2: A little but better, (+) 3: Somewhat better, (+) 4: Moderately better, (+) 5: Quite a bit better, (+) 6: A great deal better, (+) 7: A very great deal better.	3-months
Global Rate of Change Score at 6-months Post-Injection	Global Rating of Change (GROC) is scored on a Likert Scale ranging from -7 to 7, indicating a range of self-perceived overall change in function at that time point compared to the baseline. Positive higher numbers indicate positive (improvement) and negative lower numbers indicate negative (decline). The participant chooses one number on the scale. Score ranges: (-) 7: A very great deal worse, (-) 6: A great deal worse, (-) 5: Quite a bit worse, (-) 4: Moderately worse, (-) 3: Somewhat worse, (-) 2: A little bit worse, (-) 1: A tiny bit worse (almost the same), (+) 1: A tiny bit better (almost the same), (+) 2: A little but better, (+) 3: Somewhat better, (+) 4: Moderately better, (+) 5: Quite a bit better, (+) 6: A great deal better, (+) 7: A very great deal better.	6-months
Global Rate of Change Score 12-months Post-Injection	Global Rating of Change (GROC) is scored on a Likert Scale ranging from -7 to 7, indicating a range of self-perceived overall change in function at that time point compared to the baseline. Positive higher numbers indicate positive (improvement) and negative lower numbers indicate negative (decline). The participant chooses one number on the scale. Score ranges: (-) 7: A very great deal worse, (-) 6: A great deal worse, (-) 5: Quite a bit worse, (-) 4: Moderately worse, (-) 3: Somewhat worse, (-) 2: A little bit worse, (-) 1: A tiny bit worse (almost the same), (+) 1: A tiny bit better (almost the same), (+) 2: A little but better, (+) 3: Somewhat better, (+) 4: Moderately better, (+) 5: Quite a bit better, (+) 6: A great deal better, (+) 7: A very great deal better.	12-months
Global Rate of Change Score at 24-months Post-Injection	Global Rating of Change (GROC) is scored on a Likert Scale ranging from -7 to 7, indicating a range of self-perceived overall change in function at that time point compared to the baseline. Positive higher numbers indicate positive (improvement) and negative lower numbers indicate negative (decline). The participant chooses one number on the scale. Score ranges: (-) 7: A very great deal worse, (-) 6: A great deal worse, (-) 5: Quite a bit worse, (-) 4: Moderately worse, (-) 3: Somewhat worse, (-) 2: A little bit worse, (-) 1: A tiny bit worse (almost the same), (+) 1: A tiny bit better (almost the same), (+) 2: A little but better, (+) 3: Somewhat better, (+) 4: Moderately better, (+) 5: Quite a bit better, (+) 6: A great deal better, (+) 7: A very great deal better.	24-months
Duty Status at Baseline	Question asked to military service members about their current duty status.	baseline
Duty Status at 8-weeks Post-Injection	Question asked to military service members about their current duty status.	8-weeks
Duty Status at 3-months Post-Injection	Question asked to military service members about their current duty status.	3-months
Duty Status at 6-months Post-Injection	Question asked to military service members about their current duty status.	6-months
Duty Status at 12-months Post-Injection	Question asked to military service members about their current duty status.	12-months
Duty Status at 24-months Post-Injection	Question asked to military service members about their current duty status.	24-months
Patient Specific Functional Scale Scores at Baseline	Individuals are asked to self-assess limited activities and measure them on a scale from 0-10 where '0' indicates they are able to perform the activity and '10' indicates that they are unable to perform the activity prior to their condition. The reported values represent an average across all activities.	baseline
Patient Specific Functional Scale Scores at 8-weeks Post-Injection	Individuals are asked to self-assess limited activities and measure them on a scale from 0-10 where '0' indicates they are able to perform the activity and '10' indicates that they are unable to perform the activity prior to their condition. The reported values represent an average across all activities.	8-weeks
Patient Specific Functional Scale Scores at 3-months Post-Injection	Individuals are asked to self-assess limited activities and measure them on a scale from 0-10 where '0' indicates they are able to perform the activity and '10' indicates that they are unable to perform the activity prior to their condition. The reported values represent an average across all activities.	3-months
Patient Specific Functional Scale Scores at 6-months Post-Injection	Individuals are asked to self-assess limited activities and measure them on a scale from 0-10 where '0' indicates they are able to perform the activity and '10' indicates that they are unable to perform the activity prior to their condition. The reported values represent an average across all activities.	6-months
Patient Specific Functional Scale Scores at 12-months Post-Injection	Individuals are asked to self-assess limited activities and measure them on a scale from 0-10 where '0' indicates they are able to perform the activity and '10' indicates that they are unable to perform the activity prior to their condition. The reported values represent an average across all activities.	12-months
Patient Specific Functional Scale Scores at 24-months Post-Injection	Individuals are asked to self-assess limited activities and measure them on a scale from 0-10 where '0' indicates they are able to perform the activity and '10' indicates that they are unable to perform the activity prior to their condition. The reported values represent an average across all activities.	24-months
Balance Error Scoring System Score at Baseline	The Balance Error Scoring System (BESS) is scored based on a cumulative score comprised of six testing conditions, each scored based the amount of errors committed during a testing condition. Each test has a maximum of 10 errors, resulting in a total score ranging from 0 to 60 with higher scores indicating more committed mistakes and poorer balance.	baseline
Balance Error Scoring System Score at 8-weeks Post-Injection	The Balance Error Scoring System (BESS) is scored based on a cumulative score comprised of six testing conditions, each scored based the amount of errors committed during a testing condition. Each test has a maximum of 10 errors, resulting in a total score ranging from 0 to 60 with higher scores indicating more committed mistakes and poorer balance.	8-weeks
Balance Error Scoring System Score at 3-months Post-Injection	The Balance Error Scoring System (BESS) is scored based on a cumulative score comprised of six testing conditions, each scored based the amount of errors committed during a testing condition. Each test has a maximum of 10 errors, resulting in a total score ranging from 0 to 60 with higher scores indicating more committed mistakes and poorer balance.	3-months
Balance Error Scoring System Score at 6-months Post-Injection	The Balance Error Scoring System (BESS) is scored based on a cumulative score comprised of six testing conditions, each scored based the amount of errors committed during a testing condition. Each test has a maximum of 10 errors, resulting in a total score ranging from 0 to 60 with higher scores indicating more committed mistakes and poorer balance.	6-months
Balance Error Scoring System Score at 12-months Post-Injection	The Balance Error Scoring System (BESS) is scored based on a cumulative score comprised of six testing conditions, each scored based the amount of errors committed during a testing condition. Each test has a maximum of 10 errors, resulting in a total score ranging from 0 to 60 with higher scores indicating more committed mistakes and poorer balance.	12-months
Gait Analysis - Cadence at Baseline	Using wearable technology and slow motion capture camera, gait analysis will be collected. Post-run, cadence was calculated by testing administrators by reviewing the video captured to count the steps performed over the course of ten seconds. The count over the course of ten seconds was then multiplied by six to serve as a measurement for the unit of steps per minute using previously validated estimation methods.	Baseline
Ability to Run 2 Miles at Baseline	Question asked to military service members about their ability to run 2 miles.	baseline
Ability to Run 2 Miles at 8-weeks Post-Injection	Question asked to military service members about their ability to run 2 miles.	8-weeks
Ability to Run 2 Miles at 3-months Post-Injection	Question asked to military service members about their ability to run 2 miles.	3-months
Ability to Run 2 Miles at 6-months Post-Injection	Question asked to military service members about their ability to run 2 miles.	6-months
Ability to Run 2 Miles at 12-months Post-Injection	Question asked to military service members about their ability to run 2 miles.	12-months
Ability to Run 2 Miles at 24-months Post-Injection	Question asked to military service members about their ability to run 2 miles.	24-months
Gait Analysis - Cadence at 8-weeks Post-Injection	Using wearable technology and slow motion capture camera, gait analysis will be collected. Post-run, cadence was calculated by testing administrators by reviewing the video captured to count the steps performed over the course of ten seconds. The count over the course of ten seconds was then multiplied by six to serve as a measurement for the unit of steps per minute using previously validated estimation methods.	8-Weeks
Gait Analysis - Cadence at 3-months Post-Injection	Using wearable technology and slow motion capture camera, gait analysis will be collected. Post-run, cadence was calculated by testing administrators by reviewing the video captured to count the steps performed over the course of ten seconds. The count over the course of ten seconds was then multiplied by six to serve as a measurement for the unit of steps per minute using previously validated estimation methods.	3-months
Gait Analysis - Cadence at 6-months Post-Injection	Using wearable technology and slow motion capture camera, gait analysis will be collected. Post-run, cadence was calculated by testing administrators by reviewing the video captured to count the steps performed over the course of ten seconds. The count over the course of ten seconds was then multiplied by six to serve as a measurement for the unit of steps per minute using previously validated estimation methods.	6-months
Gait Analysis - Cadence at 12-months Post-Injection	Using wearable technology and slow motion capture camera, gait analysis will be collected. Post-run, cadence was calculated by testing administrators by reviewing the video captured to count the steps performed over the course of ten seconds. The count over the course of ten seconds was then multiplied by six to serve as a measurement for the unit of steps per minute using previously validated estimation methods.	12-months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability to Perform Service Specific Job Tasks at Baseline	Question that asks the military service member of their ability to perform service specific job tasks.	baseline
Ability to Perform Service Specific Job Tasks at 8-weeks Post-Injection	Question that asks the military service member of their ability to perform service specific job tasks.	8-weeks
Ability to Perform Service Specific Job Tasks at 3-months Post-Injection	Question that asks the military service member of their ability to perform service specific job tasks.	3-months
Ability to Perform Service Specific Job Tasks at 6-months Post-Injection	Question that asks the military service member of their ability to perform service specific job tasks.	6-months
Ability to Perform Service Specific Job Tasks at 12-months Post-Injection	Question that asks the military service member of their ability to perform service specific job tasks.	12-months
Ability to Perform Service Specific Job Tasks at 24-months Post-Injection	Question that asks the military service member of their ability to perform service specific job tasks.	24-months
Pain Running 2 Miles at Baseline	Pain will be measured using the Numeric Pain Rating Scale (NPRS); An 11 point Likert Scale ranging from 0 to 10 with which participants are asked to rate their pain after completing a 2-mile run. Higher numbers approaching 10 indicate greater, more severe pain, whereas lower numbers approaching 0 indicate reduced or absence of pain.	baseline
Pain Running 2 Miles at 8-weeks Post-Injection	Pain will be measured using the Numeric Pain Rating Scale (NPRS); An 11 point Likert Scale ranging from 0 to 10 with which participants are asked to rate their pain after completing a 2-mile run. Higher numbers approaching 10 indicate greater, more severe pain, whereas lower numbers approaching 0 indicate reduced or absence of pain	8-weeks
Pain Running 2 Miles at 3-months Post-Injection	Pain will be measured using the Numeric Pain Rating Scale (NPRS); An 11 point Likert Scale ranging from 0 to 10 with which participants are asked to rate their pain after completing a 2-mile run. Higher numbers approaching 10 indicate greater, more severe pain, whereas lower numbers approaching 0 indicate reduced or absence of pain.	3-months
Pain Running 2 Miles at 6-months Post-Injection	Pain will be measured using the Numeric Pain Rating Scale (NPRS); An 11 point Likert Scale ranging from 0 to 10 with which participants are asked to rate their pain after completing a 2-mile run. Higher numbers approaching 10 indicate greater, more severe pain, whereas lower numbers approaching 0 indicate reduced or absence of pain.	6-months
Pain Running 2 Miles at 12-months Post-Injection	Pain will be measured using the Numeric Pain Rating Scale (NPRS); An 11 point Likert Scale ranging from 0 to 10 with which participants are asked to rate their pain after completing a 2-mile run. Higher numbers approaching 10 indicate greater, more severe pain, whereas lower numbers approaching 0 indicate reduced or absence of pain.	12-months
Pain Running 2 Miles at 24-months Post-Injection	Pain will be measured using the Numeric Pain Rating Scale (NPRS); An 11 point Likert Scale ranging from 0 to 10 with which participants are asked to rate their pain after completing a 2-mile run. Higher numbers approaching 10 indicate greater, more severe pain, whereas lower numbers approaching 0 indicate reduced or absence of pain.	24-months
Patient Satisfaction of Treatment at 8-week Post-Injection	Questionnaire asking the individual to rate their satisfaction of treatment by choosing one option from the following scale: (1): Exceptional, (2): Excellent, (3): Very Good, (4): Good, (5): Fair, (6): Poor, (7): Very Poor.	8-weeks
Patient Satisfaction of Treatment at 3-months Post-Injection	Questionnaire asking the individual to rate their satisfaction of treatment by choosing one option from the following scale: (1): Exceptional, (2): Excellent, (3): Very Good, (4): Good, (5): Fair, (6): Poor, (7): Very Poor.	3-months
Patient Satisfaction of Treatment at 6-months Post-Injection	Questionnaire asking the individual to rate their satisfaction of treatment by choosing one option from the following scale: (1): Exceptional, (2): Excellent, (3): Very Good, (4): Good, (5): Fair, (6): Poor, (7): Very Poor.	6-months
Patient Satisfaction of Treatment at 12-weeks Post-Injection	Questionnaire asking the individual to rate their satisfaction of treatment by choosing one option from the following scale: (1): Exceptional, (2): Excellent, (3): Very Good, (4): Good, (5): Fair, (6): Poor, (7): Very Poor.	12-months
Patient Satisfaction of Treatment at 24-months Post-Injection	Questionnaire asking the individual to rate their satisfaction of treatment by choosing one option from the following scale: (1): Exceptional, (2): Excellent, (3): Very Good, (4): Good, (5): Fair, (6): Poor, (7): Very Poor.	24-months

Collaborators and Investigators

• Sponsor: Walter Reed National Military Medical Center
• Collaborators: Uniformed Services University of the Health Sciences
• Investigators: Principal Investigator: Jeffrey Leggit, MD, Uniformed Services University of the Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2020
• Primary Completion (Actual): December 6, 2024
• Study Completion (Actual): December 6, 2024

Study Registration Dates

• First Submitted: May 7, 2020
• First Submitted That Met QC Criteria: May 26, 2020
• First Posted (Actual): June 1, 2020

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: botulinum toxin, gait training, military
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Vascular Diseases; Cardiovascular Diseases; Muscular Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Compartment Syndromes; Pathological Conditions, Signs and Symptoms; Chronic Exertional Compartment Syndrome; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Hydrolases; Enzymes; Enzymes and Coenzymes; Inorganic Chemicals; Chlorine Compounds; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Metalloproteases; Bacterial Proteins; Bacterial Toxins; Toxins, Biological; Sodium Compounds; Chlorides; Hydrochloric Acid; Botulinum Toxins; Sodium Chloride
• Other Study ID Numbers: WRNMMC-2019-0266

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No