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

NCT04409600 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: WRNMMC-2019-0266
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Chronic Exertional Compartment Syndrome

Keywords

botulinum toxin, gait training, military

Outcome Measures

Primary Outcomes (45)

• 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 Outcomes (17)

• Ability to Perform Service Specific Job Tasks at Baseline

  baseline

• Ability to Perform Service Specific Job Tasks at 8-weeks Post-Injection

  8-weeks

• Ability to Perform Service Specific Job Tasks at 3-months Post-Injection

  3-months

• Ability to Perform Service Specific Job Tasks at 6-months Post-Injection

  6-months

• Ability to Perform Service Specific Job Tasks at 12-months Post-Injection

  12-months

Study Arms (4)

Home Based Gait Retraining + Saline Injection

ACTIVE COMPARATOR

Behavioral: Home Based Gait Retraining; Drug: Saline Injection

Home Based Gait Retraining + Botulinum Toxin Injection

EXPERIMENTAL

Behavioral: Home Based Gait Retraining; Drug: Botulinum Toxin Injection

Supervised Gait Retraining + Saline Injection

ACTIVE COMPARATOR

Behavioral: Supervised Gait Retraining; Drug: Saline Injection

Supervised Gait Retraining + Botulinum Toxin Injection

EXPERIMENTAL

Behavioral: Supervised Gait Retraining; Drug: Botulinum Toxin Injection

Interventions

Saline Injection DRUG

The participant will receive a saline injection to their painful lower leg compartment(s).

Home Based Gait Retraining + Saline Injection; Supervised Gait Retraining + Saline Injection

Botulinum Toxin Injection DRUG

The participant will receive a botulinum toxin injection to their painful lower leg compartment(s).

Home Based Gait Retraining + Botulinum Toxin Injection; Supervised Gait Retraining + Botulinum Toxin Injection

Supervised Gait Retraining BEHAVIORAL

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.

Supervised Gait Retraining + Botulinum Toxin Injection; Supervised Gait Retraining + Saline Injection

Home Based Gait Retraining BEHAVIORAL

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.

Home Based Gait Retraining + Botulinum Toxin Injection; Home Based Gait Retraining + Saline Injection

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Walter Reed National Military Medical Center: lead
• Uniformed Services University of the Health Sciences: collaborator

Study Sites (4)

Walter Reed National Military Medical Center

Bethesda, Maryland, 20307, United States

Location

Womack Army Medical Center

Fort Bragg, North Carolina, 28310, United States

Location

Carl R. Darnell Army Medical Center

Killeen, Texas, 76544, United States

Location

Fort Belvoir Community Hospital

Fort Belvoir, Virginia, 22060, United States

Location

MeSH Terms

Conditions

Chronic Exertional Compartment Syndrome

Interventions

Sodium Chloride; Botulinum Toxins

Condition Hierarchy (Ancestors)

Compartment Syndromes; Muscular Diseases; Musculoskeletal Diseases; Vascular Diseases; Cardiovascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Teonette Velasco, Associate Investigator
• Organization: The Geneva Foundation

tvelasco@genevausa.org

703-634-9457

Study Officials

• Jeffrey Leggit, MD

  Uniformed Services University of the Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants are masked to treatment injection arm. At 3 months post-injection, the treatment injection arm will be revealed to the participant.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2020
• First Posted: June 1, 2020
• Study Start: November 5, 2020
• Primary Completion: December 6, 2024
• Study Completion: December 6, 2024
• Last Updated: March 6, 2026
• Results First Posted: March 6, 2026

Record last verified: 2025-03

Locations

US (4)