Treatment of Lower Leg Anterolateral Chronic Exertional Compartment Syndrome With Intra-muscular Botulinum Injections.

May 16, 2023 updated by: University of Calgary

The goal of this pilot triple-blind randomized clinical trial is to determine the effectiveness of intra-muscular botulism injection for treatment of lower leg anterolateral chronic exertional compartment syndrome (CECS).

Primary Research Question: What is the effectiveness of intra-muscular botulinum injection, compared to normal saline placebo, for reducing pain related to painful sport activity in patients with lower leg anterolateral chronic exertional compartment syndrome (CECS), over a 24-week period?

Secondary outcomes will measure the time to initial onset and duration of pain during the painful sport activity, characterize the type of pain, foot paraesthesias, self-reported ankle instability, and ankle dorsiflexion and eversion muscle power. The Single Assessment Numeric Evaluation (SANE) score will provide a measure of overall leg function.

Adult patients with a confirmed diagnosis of anterolateral CECS, as determined by post-exertional compartment pressure measurements, will be invited to participate in the study. Using concealed, consecutively-numbered randomization envelopes, participants will be randomly assigned to receive either the botulinum (treatment) or the normal saline (control) injection. Participants will answer a web-based outcome questionnaire at Baseline (prior to receiving the injection) and at 2, 4, 6, 8, 12, 16, 24-weeks follow-up. Participants will be asked to do their painful sport activity the day before completing the questionnaire. Ankle dorsiflexion and eversion muscle power will be manually measured by a physiatrist in clinic at 6, 16 and 24-week follow-up visits.

Study Overview

Detailed Description

Chronic exertional compartment syndrome (CECS) of the lower leg muscle compartments is a common problem in the active population. The condition often significantly restricts patients from participating in their desired activity to the best of their ability. The pathology of CECS is related to increased intra-muscular pressure related to a restrictive fascia (envelope around the muscle or muscle group). The current standard of care for definitive treatment of CECS is a surgical fasciotomy. However, there have been a number of case reports reporting successful reduction of the symptoms of CECS with intra-muscular botulinum injections. Intra-muscular botulinum injections may reduce the symptoms of CECS by potentially decreasing muscle activation, therefore diminishing blood flow, which may reduce intra-compartmental muscle expansion and pressure of the compartment during exercise. Thus botulinum injections might provide a non-operative method of treating CECS.

This study will determine the effectiveness of intra-muscular botulinum injection, compared to a normal saline placebo, for treatment of lower leg anterolateral CECS, over a 24-week period. Participants will answer a web-based questionnaire before receiving the injection (Baseline) and at regular follow-up intervals at 2, 4, 6, 8, 12, 16, 24-weeks post-injection. The questionnaires will ask the participant to provide detailed information about their painful sport activity, and the maximum level of pain that they experience during that activity. They will also characterize the type of pain experienced, record the time to initial onset and duration of pain during the painful sport activity, and provide an overall measure of their leg function using a Single Assessment Numeric Evaluation (SANE) score. Participants will also attend an in-person appointment in clinic at Baseline, and at 6, 16 and 24-weeks post-injection for assessment of numbness and/or tingling in the foot, ankle instability, and manual ankle muscle power.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Confirmed diagnosis of lower leg anterolateral chronic exertional compartment syndrome (CECS), as measured post-exertional compartment pressure measurements of greater than 30 mmHg for immediate post-exertional compartment pressure, and greater than 12 mmHg at 5 minutes after stopping exercise.

Exclusion Criteria:

  • Female patients who are pregnant, trying to get pregnant or lactating
  • History of keloidal scarring
  • History of any significant neurologic disease (ie: amyotrophic lateral sclerosis, motor neuropathy, myasthenia gravis, Lambert-Eaton syndrome)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Treatment
Botulinum toxin (Botox) injection
Botulinum injections will be prepared by diluting 100 units of botulinum toxin A with 5.0mL of saline (20.0U/mL). A total of 100 units (5.0mL) of botulinum toxin A will be injected into the tibialis anterior, peroneus longus and peroneus brevis muscles of the affected leg. Under ultrasound guidance, the injectant will be deposited at two sites in each muscle near the motor points.
Other Names:
  • Botox
Placebo Comparator: Control
Normal saline injection
A total of 5.0mL of normal saline will be injected into the tibialis anterior, peroneus longus and peroneus brevis muscles of the affected leg. Under ultrasound guidance, the injectant will be deposited at two sites in each muscle near the motor points.
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in maximum level of pain at time of painful sport activity from Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Time Frame: Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Pain measured on a visual analog scale from 0 to 100, where 0 represents no pain and 100 represents pain as bad as it can be
Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in time to onset of pain during sport activity (minutes)
Time Frame: Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Comparison of time to onset of pain during sport activity (minutes) at Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Change in duration of exercise before having to stop due to pain (minutes)
Time Frame: Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Comparison of duration of exercise before having to stop due to pain (minutes) at Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Change in duration of pain after stopping painful exercises (minutes)
Time Frame: Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Comparison of duration of pain after stopping painful exercises (minutes) at Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Change in the numbness and/or tingling in foot during painful exercises from Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Time Frame: Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Presence or absence of numbness and/or tingling in foot during painful exercises
Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Change in ankle dorsiflexion muscle power from Baseline to 6, 16 and 24-weeks post-injection
Time Frame: Baseline, and 6, 16 and 24-weeks post-injection

Manual ankle dorsiflexion muscle power test, graded on the following scale:

0 No muscle activation

  1. Flicker of contraction, but no movement of the ankle joint
  2. Dorsiflexion of the foot with the effect of gravity eliminated
  3. Dorsiflexion of the foot against gravity but no added resistance
  4. Dorsiflexion of the foot against gravity and moderate resistance
  5. Dorsiflexion of the foot against gravity and full resistance
Baseline, and 6, 16 and 24-weeks post-injection
Ankle eversion muscle power
Time Frame: Baseline, and 6, 16 and 24-weeks post-injection

Manual ankle eversion muscle power test, graded on the following scale:

0 No muscle activation

  1. Flicker of contraction, but no movement of the ankle joint
  2. Eversion of the foot with the effect of gravity eliminated
  3. Eversion of the foot against gravity but no added resistance
  4. Eversion of the foot against gravity and moderate resistance
  5. Eversion of the foot against gravity and full resistance
Baseline, and 6, 16 and 24-weeks post-injection
Change in Single Assessment Numeric Evaluation (SANE) from Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Time Frame: Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Comparison from Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection for self-assessed rating of overall leg function using a Visual Analog Scale response, where 0 is severely abnormal and 100 is completely normal.
Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Change in ankle instability from Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Time Frame: Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Change in patient-reported assessment of presence or absence of ankle instability from Baseline to 2, 4, 6, 8, 12, 16 and 24-weeks post-injection
Baseline, and 2, 4, 6, 8, 12, 16 and 24-weeks post-injection

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Victor Lun, University of Calgary Sport Medicine Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 1, 2023

Primary Completion (Anticipated)

October 1, 2023

Study Completion (Anticipated)

June 1, 2024

Study Registration Dates

First Submitted

February 15, 2023

First Submitted That Met QC Criteria

February 28, 2023

First Posted (Actual)

March 13, 2023

Study Record Updates

Last Update Posted (Actual)

May 17, 2023

Last Update Submitted That Met QC Criteria

May 16, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Requests for individual participant data will be considered upon request.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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